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Identification of important invasion and proliferation related genes in adrenocortical carcinoma

Ali Mohamed Alshabi1(D . Basavaraj Vastrad2D . Ibrahim Ahmed Shaikh3D . Chanabasayya Vastrad4D

Received: 7 May 2019 / Accepted: 1 July 2019 @ Springer Science+Business Media, LLC, part of Springer Nature 2019

Abstract

Adrenocortical carcinoma (ACC) is an end-stage hormonal syndrome. Although profound attempts have been made to illuminate the pathogenesis, the molecular mechanisms of ACC remain to be clarified. To identify the important genes in the progression of ACC, microarray datasets GSE19775 was downloaded from the gene expression omnibus database. The differentially-expressed genes (DEGs) were identified, and pathway and GO enrichment analyses were performed. The pro- tein-protein interaction (PPI) network was constructed and the module analysis was performed using the protein interaction network analysis and Cytoscape. Also constructed target genes-miRNA regulatory network and target genes-TF regulatory network. Correlation of the hub genes were analyzed in The Cancer Genome Atlas. The prognostic values of hub genes were further validated by online tool UALCAN. Mutation analysis was done by online tool CBio Cancer Genomics Portal. A total of 884 DEGs were identified, with 441 in up regulation and 443 in down regulation. Pathways in catecholamine biosynthesis, aldosterone synthesis and secretion, pyrimidine deoxyribonucleosides salvage and systemic lupus erythematosus were the most significantly enriched for DEGs (up and down regulated). Blood vessel morphogenesis and cell cycle phase transition were the most significantly enriched term in biological processes, while extracellular matrix and chromosome, centromeric region were in cellular component and heparin binding and protein dimerization activity were in molecular function. Among the PPI networks and its module, target genes-miRNA regulatory network and target genes-TF regulatory network, hub genes were YWHAZ, FN1, GRK5, VCAM1, GATA6, TXNIP, HSPA1A, and F11R. Hub genes such as YWHAZ, STAT1, ICAM1, SH3BP5, CD83, FN1, TK1, HIST1H1C, CABLES1, and MCM3 were associated with poor overall survival, while hub genes such as STAT1, ICAM1, CD83, FN1, TK1, HIST1H1C, and MCM3 were highly expressed in stage 4. In conclu- sion, DEGs and hub genes diagnosed in this study may deepen our understanding of molecular mechanisms underlying the progression of ACC, and provide important targets for diagnosis and treatment of ACC.

Keywords Adrenocortical carcinoma · Bioinformatics analysis · Differentially-expressed genes · PPI network · Survival analysis

☒ Chanabasayya Vastrad channu.vastrad@gmail.com

1 Department of Clinical Pharmacy, College of Pharmacy, Najran University, Najran, Saudi Arabia

2 Department of Pharmaceutics, SET’S College of Pharmacy, Dharwad, Karnataka 580002, India

3 Department of Pharmacology, College of Pharmacy, Najran University, Najran, Saudi Arabia

4 Biostatistics and Bioinformatics, Chanabasava Nilaya, Bharthinagar, Dharwad, Karanataka 580001, India

Introduction

Adrenocortical carcinoma (ACC) is rare tumor cell form in the outer layer of the adrenal gland. 0.02-0.2% ACC related deaths were reported each year in the world [1]. 5-year survival rate of ACC patients was 16-47% [2]. Due to the inadequate diagnostic methods and tools, ACC is often diag- nosed at an advanced stage. Despite the key improvements in surgical treatment, the 5-year survival rate for ACC patients diagnosed with metastatic is still low at approximately 33% [3]. Thus, it’s urgently needed for compassionate the molec- ular mechanisms of ACC progression and recognition of novel biomarkers and pathways are used for the early detec- tion and prognosis assessment of ACC.

Over the past decades, advance of molecular biology have increased our compassionate of the pathogenesis of ACC. Earlier researches have indicated that ACC is a genetic dis- ease, which depends on modification of several of oncogenes and tumor suppressor genes [4]. A growing number of genes and their coding proteins related to ACC have been exam- ined. Earlier studies reported that they play key roles in a large number of physiological and pathological processes including cell proliferation [5], differentiation [6], apopto- sis [7], and metastasis [8]. However, the precise molecular mechanisms of ACC are still far from being deep under- stood. Newly, several studies have identified a group of ACC related candidate biomarkers and pathways by microarray analysis [9]. Genes such as PDL1 [10], IGF and IGFBP [11], TARBP2 [12], IGFII and MIB1 [13], and TOP2A [14] were responsible for pathogenesis of ACC. Pathways such as Wnt/ beta-catenin pathway [15], TGF-ß pathway [16], and mTOR pathway [17] were important for progression of ACC. How- ever, few studies have assessed the key genes associated in ACC using a bioinformatics approach. Accordingly, it was crucial to explore the molecular mechanisms in ACC and to detect novel and specific biomarkers, pathways, and targets.

In this study, we have downloaded GSE19775 from gene expression omnibus (GEO) database and utilized limma R bioconductor tool to identify the DEGs between ACC and normal whole adrenal gland. Additionally, other approaches including pathway enrichment analysis from different path- way databases, Gene Ontology (GO) enrichment analysis, protein-protein interaction (PPI) network construction, sub- modules analysis, target genes-miRNA, interaction con- struction, target genes-TF interaction construction, survival analysis, and validation of hub genes. The aims of our study were to identify novel biomarkers, pathways, and potential therapeutic targets for ACC.

Materials and methods

Data collection

The gene expression profile (GSE19775) included 15 ACC samples and 15 normal whole adrenal gland samples based on platform of GPL887Agilent-012097 Human 1A Micro- array (V2) G4110B (Feature Number version) was down- loaded from the GEO (http://www.ncbi.nlm.nih.gov/geo/) database, which was deposited by Demeure et al. [18].

Identification of DEGs

We utilized the “limma” R bioconductor package (R Soft- ware version 3.5.2 and R Packages limma 3.38.2) [19] to screen the DEGs between ACC samples and normal whole adrenal gland samples. The FDR (false discovery rate)

P<0.05 and |log2fold change (FC)|>1.335 for up regulated genes and llog2fold change (FC)| ← 0.891 for down regu- lated genes were chosen as the cut-off criteria. FDR (false discovery rate) was applied to help correct false-positives.

Pathway enrichment analysis

BIOCYC (https://biocyc.org/) [20], Kyoto Encyclopedia of Genes and Genomes (KEGG) (http://www.genome.jp/ kegg/pathway.html) [21], Pathway Interaction Database (PID) (https://wiki.nci.nih.gov/pages/viewpage.action?pageI d=315491760) [22], REACTOME (https://reactome.org/) [23], GenMAPP (http://www.genmapp.org/) [24], MSigDB C2 BIOCARTA (v6.0) (http://software.broadinstitute. org/gsea/msigdb/collections.jsp) [25], PantherDB (http:// www.pantherdb.org/) [26], Pathway Ontology (http://www. obofoundry.org/ontology/pw.html) [27], and Small Mol- ecule Pathway Database (SMPDB) (http://smpdb.ca/) [28] were reference knowledge bases involving systems infor- mation, genomic information, and chemical information. To further explore the biological significance of DEGs, we used a online tool ToppCluster ToppCluster (https:// toppcluster.cchmc.org/) [29] with the ability to analyze and visualize data to perform enrichment analysis of path- ways. P value <0.05 was considered a significant pathway enrichment.

Gene ontology (GO) enrichment analysis

Gene ontology (GO) (http://www.geneontology.org/) [30] is frequently used to annotate genes from high-throughput genome or transcriptome data. ToppCluster (https://toppc luster.cchmc.org/) [29] is an online functional annotation tool for multiple genes or proteins. P value <0.05 was con- sidered a significant GO enrichment.

PPI network and sub-modules analysis

Protein interaction network analysis (PINA) (http://omics .bjcancer.org/pina/home.do) [31] is an online software that contains comprehensive information of multiple proteins and is mainly used to evaluate the PPI information and this soft- ware integrates different PPI databases such as IntAct (https ://www.ebi.ac.uk/intact/) [32], Molecular INTeraction Data- base (MINT, https://mint.bio.uniroma2.it/) [33], Biological General Repository for Interaction Datasets (BioGRID, https ://thebiogrid.org/) [34], Database of Interacting Proteins (DIP, https://dip.doe-mbi.ucla.edu/dip/Main.cgi) [35], and Human Protein Reference Database (HPRD, http://www. hprd.org/) [36]. Cytoscape (http://www.cytoscape.org/) [37] version (3.7.1) was used to visualize the PPI networks of both up and down regulated genes. Confidence score ≥0.4 and maximum number of interactors = 0 were selected as

the cut-off criteria. Five topological properties such as node degree [38], betweenness [39], stress [40], closeness [41], and clustering coefficient [42] were calculated in PPI net- works. PEWCC1 [43] java plug-in of Cytoscape was utilized to illuminate the biological significance of gene modules in colon cancer with degree cut-off =2, node score cut- off=0.2, k-core=2, and max. depth=100.

Construction of target genes-miRNA regulatory network

Regulatory relationship between target genes (up and down regulated) and miRNA using online tool miRNet (https:// www.mirnet.ca/) [44] which integrates 10 miRNA databases such as TarBase (http://diana.imis.athena-innovation.gr/ DianaTools/index.php?r=tarbase/index) [45], miRTarBase (http://mirtarbase.mbc.nctu.edu.tw/php/download.php) [46], miRecords (http://miRecords.umn.edu/miRecords) [47], miR2Disease (http://www.mir2disease.org/) [48], HMDD (http://www.cuilab.cn/hmdd) [49], PhenomiR (http://mips. helmholtz-muenchen.de/phenomir/) [50], SM2miR (http:// bioinfo.hrbmu.edu.cn/SM2miR/) [51], PharmacomiR (http://www.pharmaco-mir.org/) [52], EpimiR (http://bioin fo.hrbmu.edu.cn/EpimiR/) [53], and starBase (http://starb ase.sysu.edu.cn/) [54]. Target genes-miRNA regulatory net- work was visualized by Cytoscape (http://www.cytoscape. org/) [37].

Construction of target genes-TF regulatory network

Regulatory relationship between target genes (up and down regulated) and TF using online tool NetworkAnalyst (https ://www.networkanalyst.ca/) [55] online tool which integrates one TFs database ENCODE (https://www.encodeproject. org/pipelines/ENCPL138KID/) [56]. Target genes-TF reg- ulatory network was visualized by Cytoscape (http://www. cytoscape.org/) [37].

UALCAN (http://ualcan.path.uab.edu/cgi-bin/ualcan-res. pl) [57] is an online tool for analyzing the gene expression profiles of different tumor stages and survival analysis from the Cancer Genome Atlas (TCGA). Thus, we could verify the expression levels of hub genes in all stages of ACC as well as survival analysis based on the high and low expres- sion of hub genes in ACC. P value <0.05 was considered as having statistical significance.

Genetical modification of hub genes

Online tool CBio Cancer Genomics Portal (http://www. cbioportal.org) [58] is an open strong platform that is use full for visualization, analysis, and downloads of large-scale cancer genomic dataset of ACC. This online tool is use full for researchers to explore and compare genetic alterations across samples.

Results

Identification of DEGs

GSE19775 dataset (15 ACC samples and 15 normal whole adrenal gland samples) were first downloaded and preproc- essed (normalized) is shown in Fig. 1a and b. After preproc- essing and removing batch effects, we analyzed the DEGs of GSE19775 using the limma package, using FDR (false dis- covery rate) P<0.05 and |log2fold change (FC)|>1.335 for up regulated genes and llog2fold change (FC)| ← 0.891 for down regulated genes as the cut-off criterion. We screened 884 DEGs, including 441 up regulated genes and 443 down regulated genes in ACC samples compared to normal whole adrenal gland samples was shown in volcano plot (Fig. 2 and Table 1). The results of the cluster analysis of DEGs (up and down regulated) come to know that significant differences between the ACC samples and normal whole adrenal gland samples (Figs. 3 and 4).

Pathway enrichment analysis

Pathway enrichment analysis from different pathway data- bases (BIOCYC, KEGG, PID, REACTOME, GenMAPP, MSigDB C2 BIOCARTA, PantherDB, and SMPDB) showed that the up regulated genes were mainly associated with catecholamine biosynthesis, glucocorticoid biosynthesis, aldosterone synthesis and secretion, tyrosine metabolism, IL6-mediated signaling events, IL23-mediated signaling events, metallothioneins bind metals, metabolism of steroid hormones, steroid hormone metabolism, tyrosine metabo- lism, ensemble of genes encoding extracellular matrix and extracellular matrix-associated proteins, biosynthesis of neurotransmitters, Dopamine receptor mediated signaling pathway, adrenaline and noradrenaline biosynthesis, leptin system, insulin-like growth factor signaling, catecholamine biosynthesis, and steroidogenesis are listed in Table 2, mean while down regulated genes were mainly associ- ated with pyrimidine deoxyribonucleosides salvage, gluta- mate removal from folates, systemic lupus erythematosus, FOXM1 transcription factor network, E2F transcription factor network, SIRT1 negatively regulates rRNA Expres- sion, epigenetic regulation of gene expression, methionine

Fig. 1 Box plots of the expression profiles. A: Before normalization (red) and B: after normalization (yellow). (A1,A2, A3, A4, A5, A6, A7, A8, A9,A10, A11, A12, A13, A14, A15=adrenocortical carci-

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noma samples, B1,B2, B3, B4, B5,B6, B7, B8, B9,B10, B11, B12, B13, B14, B15=normal whole adrenal gland samples)

Fig. 2 A volcano plot of differentially-expressed genes

10.0

INSM1

BORBAPS

SLC24A2

NMD3

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SMARCAS

VSTŘ12A

1CAM

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metabolism, pyrimidine metabolism, CDK Regulation of DNA Replication, ensemble of genes encoding core extra- cellular matrix including ECM glycoproteins, collagens and proteoglycans, integrin signaling pathway, serine glycine biosynthesis, mismatch repair pathway, nucleotide exci- sion repair, and adenosine deaminase deficiency are listed in Table 3.

Gene ontology (GO) enrichment analysis

Gene ontology (GO) enrichment analysis from all three GO categories [biological process (BP), cellular component

(CC), and molecular function (MF)] showed that the up regulated genes were mainly associated with blood vessel morphogenesis, response to other organism, extracellular matrix, extracellular space, heparin binding, and G protein- coupled receptor binding are listed in Table 4, mean while down regulated genes were mainly associated with cell cycle phase transition, negative regulation of chromosome segre- gation, chromosome, centromeric region, spindle, protein dimerization activity, and protein heterodimerization activity are listed in Table 5.

Table 1 The statistical metrics for key differentially-expressed genes (DEGs)
Agiliant IdGene symbolLogFCP valueFDRT valueRegulationGene name
A_23_P100642PNMT3.8620765.33E-305.71E-265.71E-26UpHomo sapiens phenylethanolamine N-methyltransferase (PNMT), mRNA [NM_002686]
A_23_P254584PENK4.6881745.66E-305.71E-265.71E-26UpHomo sapiens proenkephalin (PENK), mRNA [NM_006211]
A_23_P167493CART4.1391773.83E-292.41E-252.41E-25UpHomo sapiens cocaine- and amphetamine-regulated tran- script (CART), mRNA [NM_004291]
A_23_P14595CHGA3.1776664.78E-292.41E-252.41E-25UpHomo sapiens chromogranin A (parathyroid secretory pro- tein 1) (CHGA), mRNA [NM_001275]
A_23_P109287GRIK12.9217071.15E-284.64E-254.64E-25UpHomo sapiens glutamate receptor, ionotropic, kainate 1 (GRIK1), transcript variant 1, mRNA [NM_000830]
A_23_P217508ZBED12.9243171.99E-286.68E-256.68E-25UpHomo sapiens zinc finger, BED domain containing 1 (ZBED1), mRNA [NM_004729]
A_23_P51376NKAIN14.6559233.29E-289.48E-259.48E-25UpSodium/potassium transporting ATPase interacting 1
A_23_P417918PENK2.9958796.47E-281.63E-241.63E-24UpHomo sapiens proenkephalin (PENK), mRNA [NM_006211]
A_23_P117095FGF231.998734.07E-269.12E-239.12E-23UpHomo sapiens fibroblast growth factor 23 (FGF23), mRNA [NM_020638]
A_23_P51132IL1RL12.5513722.39E-254.79E-224.79E-22UpHomo sapiens interleukin 1 receptor-like 1 (IL1RL1), tran- script variant 1, mRNA [NM_016232]
A_23_P109185INSM11.9817312.61E-254.79E-224.79E-22UpHomo sapiens insulinoma-associated 1 (INSM1), mRNA [NM_002196]
A_23_P112296DBH3.0321733.17E-255.33E-225.33E-22UpHomo sapiens dopamine beta-hydroxylase (dopamine beta- monooxygenase) (DBH), mRNA [NM_000787]
A_23_P93773HOXA52.1114671.31E-242.04E-212.04E-21UpHomo sapiens homeo box A5 (HOXA5), mRNA [NM_019102]
A_23_P202245M312132.8853342.83E-244.08E-214.08E-21UpHuman papillary thyroid carcinoma-encoded protein mRNA, complete cds. [M31213]
A_23_P154115IGFBP52.1530614.43E-245.96E-215.96E-21UpHomo sapiens insulin-like growth factor binding protein 5 (IGFBP5), mRNA [NM_000599]
A_23_P213228PHOX2B2.1078131.35E-231.7E-201.7E-20UpHomo sapiens paired-like homeobox 2b (PHOX2B), mRNA [NM_003924]
A_23_P38628#N/A1.7287911.02E-221.17E-191.17E-19UpUnknown
A_23_P21770SLC18A11.5415911.04E-221.17E-191.17E-19UpHomo sapiens solute carrier family 18 (vesicular monoam- ine), member 1 (SLC18A1), mRNA [NM_003053]
A_23_P145104TFAP2B2.1873231.45E-221.54E-191.54E-19UpHomo sapiens transcription factor AP-2 beta (activating enhancer binding protein 2 beta) (TFAP2B), mRNA [NM_003221]
A_23_P433050LGR71.6053854.19E-224.22E-194.22E-19UpHomo sapiens leucine-rich repeat-containing G protein- coupled receptor 7 (LGR7), mRNA [NM_021634]
A_23_P37251SNAPC11.5650128.5E-228.17E-198.17E-19UpHomo sapiens small nuclear RNA activating complex, poly- peptide 1, 43 kDa (SNAPC1), mRNA [NM_003082]
A_23_P377296ECE22.4468489.74E-228.93E-198.93E-19UpHomo sapiens endothelin converting enzyme 2 (ECE2), mRNA [NM_014693]
A_23_P12874GTPBP42.957761.11E-219.64E-199.64E-19UpHomo sapiens GTP binding protein 4 (GTPBP4), mRNA [NM_012341]
A_23_P50376ZNF3311.9272531.15E-219.64E-199.64E-19UpHomo sapiens zinc finger protein 331 (ZNF331), mRNA [NM_018555]
A_23_P159488#N/A1.9354881.74E-211.4E-181.4E-18UpUnknown
A_23_P31755CRH1.7338686.49E-215.04E-185.04E-18UpHomo sapiens corticotropin releasing hormone (CRH), mRNA [NM_000756]
A_23_P127220DNAJC123.198528.37E-216.26E-186.26E-18UpHomo sapiens DnaJ (Hsp40) homolog, subfamily C, member 12 (DNAJC12), transcript variant 1, mRNA [NM_021800]
A_23_P107201STAT31.5836321.31E-209.45E-189.45E-18UpHomo sapiens signal transducer and activator of transcription 3 (acute-phase response factor) (STAT3), transcript variant 1, mRNA [NM_139276]
A_23_P397969FOXK21.4186921.6E-201.08E-171.08E-17UpHomo sapiens forkhead box K2 (FOXK2), transcript variant 2, mRNA [NM_181430]
A_23_P55036#N/A2.0151471.6E-201.08E-171.08E-17UpUnknown
A_23_P95891TH1.3702032.07E-201.35E-171.35E-17UpHomo sapiens tyrosine hydroxylase (TH), transcript variant 3, mRNA [NM_199293]
A_23_P16834FNDC42.0924422.89E-201.82E-171.82E-17UpHomo sapiens fibronectin type III domain containing 4 (FNDC4), mRNA [NM_022823]
Table 1 (continued)
Agiliant IdGene symbolLogFCP valueFDRT valueRegulationGene name
A_23_P375404SLC25A191.9243953.97E-202.43E-172.43E-17UpHomo sapiens solute carrier family 25 (mitochondrial deoxynucleotide carrier), member 19 (SLC25A19), mRNA [NM_021734]
A_23_P74508THC21327061.9229965.36E-203.18E-173.18E-17UpQ92681 (Q92681) Sodium-D-glucose cotransporter, complete [THC2132706]
A_23_P209861TLX21.9357977.24E-204.17E-174.17E-17UpT-cell leukemiahomeobox protein 2 (Homeobox protein Hox- 11L1) (Neural crest homeobox protein). [Source: Uniprot/ SWISSPROT;Acc:O43763] [ENST00000233638]
A_23_P10062HGNT-IV-H1.4707121.7E-199.51E-179.51E-17UpHomo sapiens UDP-N-acetylglucosamine:a-1,3-D-mannoside beta-1,4-N-acetylglucosaminyltransferase IV (HGNT-IV- H), mRNA [NM_013244]
A_23_P433690ZNF3312.5195992.33E-191.27E-161.27E-16UpHomo sapiens zinc finger protein 331 (ZNF331), mRNA [NM_018555]
A_23_P104579DOC-1R1.4170136.1E-193.15E-163.15E-16UpHomo sapiens tumor suppressor deleted in oral cancer- related 1 (DOC-1R), mRNA [NM_005851]
A_23_P369479MSI21.7672716.28E-193.17E-163.17E-16UpHomo sapiens musashi homolog 2 (Drosophila) (MSI2), transcript variant 2, mRNA [NM_170721]
A_23_P36962DNAJC31.7222781.08E-185.16E-165.16E-16UpHomo sapiens DnaJ (Hsp40) homolog, subfamily C, member 3 (DNAJC3), mRNA [NM_006260]
A_23_P138218FMO21.6124741.1E-185.16E-165.16E-16UpDimethylanilinemonooxygenase [N-oxide-forming] 2 (EC 1.14.13.8) (Pulmonary flavin-containing monooxyge- nase 2) (FMO 2) (Dimethylaniline oxidase 2) (FMO 1B1). [Source:Uniprot/SWISSPROT;Acc:Q99518] [ENST00000209929]
A_23_P126103CTH3.8817231.27E-185.84E-165.84E-16UpHomo sapiens cystathionase (cystathionine gamma-lyase) (CTH), transcript variant 1, mRNA [NM_001902]
A_23_P56433ECRG42.0362241.3E-185.85E-165.85E-16UpHomo sapiens esophageal cancer-related gene 4 protein (ECRG4), mRNA [NM_032411]
A_23_P356616ABTB21.7273961.37E-185.91E-165.91E-16UpHomo sapiens ankyrin repeat and BTB (POZ) domain con- taining 2 (ABTB2), mRNA [NM_145804]
A_23_P209559REG-III2.4894932.11E-188.86E-168.86E-16UpHomo sapiens LPPM429 (REG-III), mRNA [NM_198448]
A_23_P162640GABARAPL11.6908062.2E-189.08E-169.08E-16UpHomo sapiens GABA(A) receptor-associated protein-like 1 (GABARAPL1), mRNA [NM_031412]
A_23_P73451#N/A2.1118013.1E-181.2E-151.2E-15UpUnknown
A_23_P21462HGNT-IV-H1.3687973.43E-181.31E-151.31E-15UpHomo sapiens UDP-N-acetylglucosamine:a-1,3-D-mannoside beta-1,4-N-acetylglucosaminyltransferase IV (HGNT-IV- H), mRNA [NM_013244]
A_23_P54992Dlc21.5068133.78E-181.41E-151.41E-15UpHomo sapiens dynein light chain 2 (Dlc2), mRNA [NM_080677]
A_23_P212119GALNTL21.50494.53E-181.66E-151.66E-15UpHomo sapiens UDP-N-acetyl-alpha- D-galactosamine:polypeptide-N-acetylgalactosaminyltrans- ferase-like 2 (GALNTL2), mRNA [NM_054110]
A_23_P200780TGFBR32.0255465.21E-181.88E-151.88E-15UpHomo sapiens transforming growth factor, beta receptor III (betaglycan, 300 kDa) (TGFBR3), mRNA [NM_003243]
A_23_P86706ZRANB11.5466217.82E-182.67E-152.67E-15UpHomo sapiens zinc finger, RAN-binding domain containing 1, mRNA (cDNA clone IMAGE:5188569), complete cds. [BC048281]
A_23_P208031SYT43.3041258.22E-182.77E-152.77E-15UpHomo sapiens synaptotagmin IV (SYT4), mRNA [NM_020783]
A_23_P143973SH3BP52.3515078.65E-182.86E-152.86E-15UpHomo sapiens SH3-domain binding protein 5 (BTK-associ- ated) (SH3BP5), mRNA [NM_004844]
A_23_P216877NR4A32.2198851.29E-174.12E-154.12E-15UpHomo sapiens nuclear receptor subfamily 4, group A, mem- ber 3 (NR4A3), transcript variant 2, mRNA [NM_173198]
A_23_P304554MRAP1.9105651.47E-174.63E-154.63E-15UpHomo sapiens chromosome 21 open reading frame 61 (C21orf61), transcript variant 2, mRNA [NM_206898]
A_23_P41188MRAS2.0288191.53E-174.73E-154.73E-15UpHomo sapiens muscle RAS oncogene homolog (MRAS), mRNA [NM_012219]
A_23_P97309CASP92.0477531.55E-174.73E-154.73E-15UpHomo sapiens caspase 9, apoptosis-related cysteine protease (CASP9), transcript variant alpha, mRNA [NM_001229]
A_23_P337849TNRC41.5847931.61E-174.85E-154.85E-15UpHomo sapiens trinucleotide repeat-containing 4 (TNRC4), mRNA [NM_007185]
A_23_P377197MRAS1.3564691.67E-174.95E-154.95E-15UpHomo sapiens muscle RAS oncogene homolog (MRAS), mRNA [NM_012219]
Table 1 (continued)
Agiliant IdGene symbolLogFCP valueFDRT valueRegulationGene name
A_23_P201979CREM2.6935381.78E-175.22E-155.22E-15UpHomo sapiens cAMP responsive element modulator (CREM), transcript variant 19, mRNA [NM_183013]
A_23_P38649MC2R1.7564791.84E-175.23E-155.23E-15UpHomo sapiens melanocortin 2 receptor (adrenocorticotropic hormone) (MC2R), mRNA [NM_000529]
A_23_P107581NPC12.1438871.98E-175.51E-155.51E-15UpHomo sapiens Niemann-Pick disease, type C1 (NPC1), mRNA [NM_000271]
A_23_P98022SIRT11.7616122.02E-175.51E-155.51E-15UpHomo sapiens sirtuin (silent mating type information regulation 2 homolog) 1 (S. cerevisiae) (SIRT1), mRNA [NM_012238]
A_23_P68007ATP1B32.3472762.21E-175.93E-155.93E-15UpHomo sapiens ATPase, Na+/K + transporting, beta 3 poly- peptide (ATP1B3), mRNA [NM_001679]
A_23_P139216H192.1257712.77E-177.31E-157.31E-15UpHomo sapiens H19, imprinted maternally expressed untrans- lated mRNA (H19) on chromosome 11 [NR_002196]
A_23_P319423KCNK51.8054232.79E-177.31E-157.31E-15UpHomo sapiens potassium channel, subfamily K, member 5 (KCNK5), mRNA [NM_003740]
A_23_P71530TNFRSF11B1.8020293.36E-178.7E-158.7E-15UpHomo sapiens tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin) (TNFRSF11B), mRNA [NM_002546]
A_23_P165598ENST000003099503.9203163.46E-178.73E-158.73E-15UpHomo sapiens full-length insert cDNA clone ZE09G12. [AF086541]
A_23_P253911CHRNA33.4231526.16E-171.53E-141.53E-14UpHomo sapiens cholinergic receptor, nicotinic, alpha polypep- tide 3 (CHRNA3), mRNA [NM_000743]
A_23_P145644DDC2.9292277.92E-171.95E-141.95E-14UpHomo sapiens dopa decarboxylase (aromatic L-amino acid decarboxylase) (DDC), mRNA [NM_000790]
A_23_P134953ADFP2.5150949.47E-172.28E-142.28E-14UpHomo sapiens adipose differentiation-related protein (ADFP), mRNA [NM_001122]
A_23_P65817GABARAPL11.4431241.36E-163.15E-143.15E-14UpHomo sapiens GABA(A) receptor-associated protein-like 1 (GABARAPL1), mRNA [NM_031412]
A_23_P105963AK71.3603861.49E-163.41E-143.41E-14UpHomo sapiens adenylate kinase 7 (AK7), mRNA [NM_152327]
A_23_P54267SCG32.5099711.84E-164.17E-144.17E-14UpHomo sapiens secretogranin III (SCG3), mRNA [NM_013243]
A_23_P364517SELK1.6770932.08E-164.62E-144.62E-14UpHomo sapiens selenoprotein K (SELK), mRNA [NM_021237]
A_23_P73517CITED12.7374992.12E-164.65E-144.65E-14UpHomo sapiens Cbp/p300-interacting transactivator, with Glu/ Asp-rich carboxy-terminal domain, 1 (CITED1), mRNA [NM_004143]
A_23_P127851FXC11.6417582.49E-165.35E-145.35E-14UpHomo sapiens fracture callus 1 homolog (rat) (FXC1), mRNA [NM_012192]
A_23_P75622ATP5L1.7484062.6E-165.46E-145.46E-14UpHomo sapiens ATP synthase, H + transporting, mitochondrial F0 complex, subunit g (ATP5L), nuclear gene encoding mitochondrial protein, mRNA [NM_006476]
A_23_P355295FMO22.4970873.31E-166.84E-146.84E-14UpHomo sapiens flavin-containing monooxygenase 2 (FMO2), mRNA [NM_001460]
A_23_P76644RAB201.760033.77E-167.6E-147.6E-14UpHomo sapiens RAB20, member RAS oncogene family (RAB20), mRNA [NM_017817]
A_23_P6951ATP1B32.411364.22E-168.34E-148.34E-14UpHomo sapiens ATPase, Na+/K + transporting, beta 3 poly- peptide (ATP1B3), mRNA [NM_001679]
A_23_P125788TCEAL72.1388334.53E-168.81E-148.81E-14UpHomo sapiens transcription elongation factor A (SII)-like 7 (TCEAL7), mRNA [NM_152278]
A_23_P101992MARCO1.7831614.54E-168.81E-148.81E-14UpHomo sapiens macrophage receptor with collagenous struc- ture (MARCO), mRNA [NM_006770]
A_23_P72097AK1242581.3644514.72E-169.07E-149.07E-14UpHomo sapiens cDNA FLJ42264 fis, clone TKIDN2014757. [AK124258]
A_23_P369201SCARB12.1723875.21E-169.91E-149.91E-14UpHomo sapiens scavenger receptor class B, member 1 (SCARB1), mRNA [NM_005505]
A_23_P68970ARFGAP32.0207775.77E-161.09E-131.09E-13UpHomo sapiens ADP-ribosylation factor GTPase activating protein 3 (ARFGAP3), mRNA [NM_014570]
A_23_P121064PTX32.49866.1E-161.13E-131.13E-13UpHomo sapiens pentaxin-related gene, rapidly induced by IL-1 beta (PTX3), mRNA [NM_002852]
A_23_P112982DKFZp761H0391.5036056.13E-161.13E-131.13E-13UpHomo sapiens hypothetical protein DKFZp761H039 (DKFZp761H039), mRNA [NM_018711]
Table 1 (continued)
Agiliant IdGene symbolLogFCP valueFDRT valueRegulationGene name
A_23_P255231TNFAIP91.5772557.53E-161.38E-131.38E-13UpHomo sapiens tumor necrosis factor, alpha-induced protein 9 (TNFAIP9), mRNA [NM_024636]
A_23_P80570AADAC3.257219.13E-161.62E-131.62E-13UpHomo sapiens arylacetamidedeacetylase (esterase) (AADAC), mRNA [NM_001086]
A_23_P207481PRO18551.7256481.22E-152.1E-132.1E-13UpHomo sapiens hypothetical protein PRO1855 (PRO1855), mRNA [NM_018509]
A_23_P129896ALDH3A21.7906671.49E-152.44E-132.44E-13UpHomo sapiens aldehyde dehydrogenase 3 family, member A2 (ALDH3A2), mRNA [NM_000382]
A_23_P95690SPOCK31.8849981.72E-152.76E-132.76E-13UpHomo sapiens sparc/osteonectin, cwcv and kazal-like domains proteoglycan (testican) 3, mRNA (cDNA clone MGC:20285 IMAGE:4110883), complete cds. [BC013983]
A_23_P133000FLJ115391.7601812.07E-153.22E-133.22E-13UpHomo sapiens cDNA FLJ11539 fis, clone HEMBA1002748. [AK021601]
A_23_P67008GATA61.4052792.77E-154.1E-134.1E-13UpH.sapiens mRNA for GATA-6 DNA binding protein. [X95701]
A_23_P168598PON13.0477422.85E-154.16E-134.16E-13UpHomo sapiens paraoxonase 1 (PON1), mRNA [NM_000446]
A_23_P436259ERN12.7534.09E-155.78E-135.78E-13UpHomo sapiens endoplasmic reticulum to nucleus signaling 1 (ERN1), transcript variant 2, mRNA [NM_152461]
A_23_P96590GPRASP12.0789824.12E-155.78E-135.78E-13UpHomo sapiens G protein-coupled receptor-associated sorting protein 1 (GPRASP1), mRNA [NM_014710]
A_23_P42257IER32.630074.33E-156.03E-136.03E-13UpHomo sapiens immediate early response 3 (IER3), transcript variant short, mRNA [NM_003897]
A_23_P113121DLG21.4155496.21E-158.35E-138.35E-13UpHomo sapiens cDNA FLJ44824 fis, clone BRACE3046491, highly similar to Channel associated protein of syn- apse-110. [AK126776]
A_23_P357207C6orf1171.686296.37E-158.51E-138.51E-13UpHomo sapiens chromosome 6 open reading frame 117 (C6orf117), mRNA [NM_138409]
A_23_P503200PHF101.5965557.65E-151E-121E-12UpHomo sapiens PHD finger protein 10 (PHF10), transcript variant 1, mRNA [NM_018288]
A_23_P118392RASD12.7447228.56E-151.11E-121.11E-12UpHomo sapiens RAS, dexamethasone-induced 1 (RASD1), mRNA [NM_016084]
A_23_P84118CDH181.988531.04E-141.34E-121.34E-12UpHomo sapiens cadherin 18, type 2 (CDH18), mRNA [NM_004934]
A_23_P218331CYB5611.5208251.14E-141.45E-121.45E-12UpHomo sapiens cytochrome b-561 (CYB561), mRNA [NM_001915]
A_23_P343671FOSL21.7259961.18E-141.5E-121.5E-12UpFos-related antigen 2. [Source:Uniprot/ SWISSPROT;Acc:P15408] [ENST00000265539]
A_23_P140469H631.3400761.22E-141.54E-121.54E-12UpHomo sapiens H63 breast cancer expressed gene (H63), transcript variant 1, mRNA [NM_138423]
A_23_P49610MGC143762.583761.5E-141.85E-121.85E-12UpHomo sapiens hypothetical protein MGC14376 (MGC14376), transcript variant 1, mRNA [NM_032895]
A_23_P167328CD381.8457081.59E-141.96E-121.96E-12UpHomo sapiens CD38 antigen (p45) (CD38), mRNA [NM_001775]
A_23_P118552HIS12.3482171.74E-142.12E-122.12E-12UpHomo sapiens HMBA-inducible (HIS1), mRNA [NM_006460]
A_23_P114708CYP4B12.2107822.04E-142.43E-122.43E-12UpHomo sapiens cytochrome P450, family 4, subfamily B, polypeptide 1 (CYP4B1), mRNA [NM_000779]
A_23_P20022HIG22.4444952.1E-142.49E-122.49E-12UpHomo sapiens hypoxia-inducible protein 2 (HIG2), mRNA [NM_013332]
A_23_P7154HAND21.920272.18E-142.57E-122.57E-12UpHeart- and neural crest derivatives-expressed pro- tein 2 (Deciduum, heart, autonomic nervous system and neural crest derivatives-expressed protein 2) (dHAND). [Source: Uniprot/SWISSPROT;Acc:P61296] [ENST00000359562]
A_23_P397455ACVR1C1.9391072.43E-142.84E-122.84E-12UpHomo sapiens activin A receptor, type IC (ACVR1C), mRNA [NM_145259]
A_23_P150693FJX11.4024162.5E-142.89E-122.89E-12UpHomo sapiens four jointed box 1 (Drosophila) (FJX1), mRNA [NM_014344]
A_23_P213857C71.8486362.51E-142.89E-122.89E-12UpHomo sapiens complement component 7 (C7), mRNA [NM_000587]
Table 1 (continued)
Agiliant IdGene symbolLogFCP valueFDRT valueRegulationGene name
A_23_P132718SEMA3B1.9620793.26E-143.7E-123.7E-12UpHomo sapiens sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3B (SEMA3B), transcript variant 1, mRNA [NM_004636]
A_23_P151525C14orf1322.3970733.52E-143.97E-123.97E-12UpHomo sapiens mRNA; cDNA DKFZp761F2014 (from clone DKFZp761F2014). [AL390130]
A_23_P129167CYP11A12.3049984.02E-144.43E-124.43E-12UpHomo sapiens cytochrome P450, family 11, subfamily A, polypeptide 1 (CYP11A1), nuclear gene encoding mito- chondrial protein, mRNA [NM_000781]
A_23_P33803C15orf121.5122734.16E-144.56E-124.56E-12UpHomo sapiens chromosome 15 open reading frame 12 (C15orf12), nuclear gene encoding mitochondrial protein, mRNA [NM_018285]
A_23_P19134MASS12.4471984.19E-144.57E-124.57E-12UpHomo sapiens monogenic, audiogenic seizure susceptibility 1 homolog (mouse) (MASS1), mRNA [NM_032119]
A_23_P319005HMP191.4070114.44E-144.79E-124.79E-12UpHomo sapiens HMP19 protein (HMP19), mRNA [NM_015980]
A_23_P107283HOXB23.3124354.64E-144.95E-124.95E-12UpHomo sapiens homeo box B2 (HOXB2), mRNA [NM_002145]
A_23_P162162KCTD141.4816754.93E-145.15E-125.15E-12UpHomo sapiens potassium channel tetramerisation domain containing 14 (KCTD14), mRNA [NM_023930]
A_23_P331598IPO71.5817365.11E-145.31E-125.31E-12UpHomo sapiens importin 7 (IPO7), mRNA [NM_006391]
A_23_P8812W607814.5913665.48E-145.64E-125.64E-12UpW60781 zd26f05.r1 Soares_fetal_heart_NbHH19 W Homo sapiens cDNA clone IMAGE:341793 5' similar to gb:J02874 FATTY ACID-BINDING PROTEIN, ADIPO- CYTE (HUMAN);, mRNA sequence [W60781]
A_23_P252825SCAP1.6233576.82E-146.88E-126.88E-12UpHomo sapiens SREBP cleavage-activating protein (SCAP), mRNA [NM_012235]
A_23_P210100CYP26B12.777587.02E-147.05E-127.05E-12UpHomo sapiens cytochrome P450, family 26, subfamily B, polypeptide 1 (CYP26B1), mRNA [NM_019885]
A_23_P79191SCG22.3232987.43E-147.39E-127.39E-12UpHomo sapiens secretogranin II (chromogranin C) (SCG2), mRNA [NM_003469]
A_23_P351724TNS1.5975818.11E-147.96E-127.96E-12UpHomo sapiens tensin (TNS), mRNA [NM_022648]
A_23_P258944DNAJB92.1110998.13E-147.96E-127.96E-12UpHomo sapiens DnaJ (Hsp40) homolog, subfamily B, member 9 (DNAJB9), mRNA [NM_012328]
A_23_P7144CXCL14.1700188.34E-148.09E-128.09E-12UpHomo sapiens chemokine (C-X-C motif) ligand 1 (melanoma growth stimulating activity, alpha) (CXCL1), mRNA [NM_001511]
A_23_P33356ADAMTS91.4762199.52E-149.15E-129.15E-12UpHomo sapiens a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 9 (ADAMTS9), transcript variant 3, mRNA [NM_020249]
A_23_P96556GK1.5774881.02E-139.71E-129.71E-12UpHomo sapiens glycerol kinase (GK), transcript variant 2, mRNA [NM_000167]
A_23_P97173HSD3B12.0792041.05E-139.93E-129.93E-12UpHomo sapiens hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1 (HSD3B1), mRNA [NM_000862]
A_23_P64617FZD42.49131.09E-131.01E-111.01E-11UpHomo sapiens frizzled homolog 4 (Drosophila) (FZD4), mRNA [NM_012193]
A_23_P119882GCKR2.320161.15E-131.07E-111.07E-11UpHomo sapiens glucokinase (hexokinase 4) regulator (GCKR), mRNA [NM_001486]
A_23_P90649IRS11.7551751.19E-131.1E-111.1E-11UpHomo sapiens insulin receptor substrate 1 (IRS1), mRNA [NM_005544]
A_23_P78998C19orf41.6751451.34E-131.23E-111.23E-11UpHomo sapiens chromosome 19 open reading frame 4, mRNA (cDNA clone MGC:17013 IMAGE:4181442), complete cds. [BC010446]
A_23_P318220SF11.446191.42E-131.28E-111.28E-11UpHomo sapiens splicing factor 1 (SF1), transcript variant 1, mRNA [NM_004630]
A_23_P170719#N/A2.2329121.49E-131.32E-111.32E-11UpUnknown
A_23_P216756FCN22.267082.21E-131.9E-111.9E-11UpHomo sapiens ficolin (collagen/fibrinogen domain containing lectin) 2 (hucolin) (FCN2), transcript variant SV2, mRNA [NM_015838]
A_23_P19592PGM31.9063722.26E-131.93E-111.93E-11UpHomo sapiens phosphoglucomutase 3 (PGM3), mRNA [NM_015599]
A_23_P51576HSD3B22.3717332.33E-131.98E-111.98E-11UpHomo sapiens hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 2 (HSD3B2), mRNA [NM_000198]
Table 1 (continued)
Agiliant IdGene symbolLogFCP valueFDRT valueRegulationGene name
A_23_P132793ARMET1.3386782.71E-132.29E-112.29E-11UpHomo sapiens arginine-rich, mutated in early stage tumors (ARMET), mRNA [NM_006010]
A_23_P46673PTP4A1P71.9091262.79E-132.34E-112.34E-11UpProtein tyrosine phosphatase type IVA, member 1 pseudo- gene 7
A_23_P20494NDRG11.6174462.87E-132.4E-112.4E-11UpHomo sapiens N-myc downstream regulated gene 1 (NDRG1), mRNA [NM_006096]
A_23_P11685PLA2G4A1.666792.94E-132.45E-112.45E-11UpHomo sapiens phospholipase A2, group IVA (cytosolic, calcium-dependent) (PLA2G4A), mRNA [NM_024420]
A_23_P340848PTGIR1.3370422.98E-132.47E-112.47E-11UpHomo sapiens prostaglandin I2 (prostacyclin) receptor (IP) (PTGIR), mRNA [NM_000960]
A_23_P107117ZNF1792.0333283.02E-132.48E-112.48E-11UpHomo sapiens zinc finger protein 179 (ZNF179), mRNA [NM_007148]
A_23_P45699FUBP11.5134423.02E-132.48E-112.48E-11UpHomo sapiens far upstream element (FUSE) binding protein 1 (FUBP1), mRNA [NM_003902]
A_23_P348121FOSL21.5699733.03E-132.49E-112.49E-11UpHomo sapiens FOS-like antigen 2 (FOSL2), mRNA [NM_005253]
A_23_P128246HYPE1.3995063.28E-132.66E-112.66E-11UpHomo sapiens Huntingtin interacting protein E (HYPE), mRNA [NM_007076]
A_23_P139669SLC2A31.5310933.62E-132.92E-112.92E-11UpHomo sapiens solute carrier family 2 (facilitated glucose transporter), member 3 (SLC2A3), mRNA [NM_006931]
A_23_P56488FLJ398221.5748173.92E-133.12E-113.12E-11UpHomo sapiens hypothetical protein FLJ39822 (FLJ39822), mRNA [NM_173512]
A_23_P14026CREBL21.9204814.37E-133.44E-113.44E-11UpHomo sapiens cAMP responsive element binding protein- like 2 (CREBL2), mRNA [NM_001310]
A_23_P103877LRRC382.9050124.44E-133.49E-113.49E-11Upleucine-rich repeat-containing 38
A_23_P131207NR4A22.9369324.47E-133.49E-113.49E-11UpHomo sapiens nuclear receptor subfamily 4, group A, mem- ber 2 (NR4A2), transcript variant 1, mRNA [NM_006186]
A_23_P169178TESK11.7435385.17E-134.01E-114.01E-11UpHomo sapiens testis-specific kinase 1 (TESK1), mRNA [NM_006285]
A_23_P207221FLJ108471.9456595.89E-134.54E-114.54E-11UpHomo sapiens hypothetical protein FLJ10847 (FLJ10847), mRNA [NM_018242]
A_23_P64721GPR109B1.4442716.47E-134.95E-114.95E-11UpHomo sapiens G protein-coupled receptor 109B (GPR109B), mRNA [NM_006018]
A_23_P128520IGFBP61.3438947.1E-135.34E-115.34E-11UpHomo sapiens insulin-like growth factor binding protein 6 (IGFBP6), mRNA [NM_002178]
A_23_P398566NR4A33.5079948.02E-135.99E-115.99E-11UpHomo sapiens nuclear receptor subfamily 4, group A, mem- ber 3 (NR4A3), transcript variant 3, mRNA [NM_173200]
A_23_P69699NPY1R3.071928.28E-136.14E-116.14E-11UpHomo sapiens neuropeptide Y receptor Y1 (NPY1R), mRNA [NM_000909]
A_23_P251841NRXN31.5416481.05E-127.58E-117.58E-11UpHomo sapiens neurexin 3 (NRXN3), transcript variant alpha, mRNA [NM_004796]
A_23_P91919SERP11.5650861.18E-128.49E-118.49E-11UpHomo sapiens stress-associated endoplasmic reticulum protein 1 (SERP1), mRNA [NM_014445]
A_23_P64138ST3GAL41.6634461.3E-129.25E-119.25E-11UpHomo sapiens sialyltransferase 4℃ (beta-galactoside alpha- 2,3-sialyltransferase) (SIAT4C), mRNA [NM_006278]
A_23_P161659SYT131.5261821.31E-129.29E-119.29E-11UpHomo sapiens synaptotagmin XIII (SYT13), mRNA [NM_020826]
A_23_P110941GSTA42.2683181.33E-129.33E-119.33E-11UpHomo sapiens glutathione S-transferase A4 (GSTA4), mRNA [NM_001512]
A_23_P811G1P22.226581.49E-121.03E-101.03E-10UpHomo sapiens interferon, alpha-inducible protein (clone IFI- 15K), mRNA (cDNA clone MGC:3945 IMAGE:3545944), complete cds. [BC009507]
A_23_P69208TIMP43.0096321.5E-121.03E-101.03E-10UpHomo sapiens tissue inhibitor of metalloproteinase 4 (TIMP4), mRNA [NM_003256]
A_23_P128166RAB211.7669471.96E-121.29E-101.29E-10UpHomo sapiens RAB21, member RAS oncogene family (RAB21), mRNA [NM_014999]
A_23_P382584CHGB4.0478182.1E-121.37E-101.37E-10UpHomo sapiens chromogranin B (secretogranin 1) (CHGB), mRNA [NM_001819]
A_23_P203751FLJ221041.3437732.17E-121.42E-101.42E-10UpHomo sapiens hypothetical protein FLJ22104 (FLJ22104), mRNA [NM_022918]
A_23_P215997CYP11B22.6220822.66E-121.71E-101.71E-10UpHomo sapiens cytochrome P450, family 11, subfamily B, polypeptide 2 (CYP11B2), nuclear gene encoding mito- chondrial protein, mRNA [NM_000498]
Table 1 (continued)
Agiliant IdGene symbolLogFCP valueFDRT valueRegulationGene name
A_23_P60166DEPDC61.8244232.81E-121.8E-101.8E-10UpHomo sapiens DEP domain containing 6 (DEPDC6), mRNA [NM_022783]
A_23_P81006IL81.6482472.92E-121.86E-101.86E-10UpHomo sapiens interleukin 8 (IL8), mRNA [NM_000584]
A_23_P41645ELL22.3229713.03E-121.91E-101.91E-10UpHomo sapiens elongation factor, RNA polymerase II, 2 (ELL2), mRNA [NM_012081]
A_23_P126486MGC127601.6975773.58E-122.22E-102.22E-10UpHomo sapiens hypothetical protein MGC12760, mRNA (cDNA clone MGC:12760 IMAGE:4111573), complete cds. [BC006312]
A_23_P109427GSTT22.4304913.64E-122.25E-102.25E-10UpHomo sapiens glutathione S-transferase theta 2 (GSTT2), mRNA [NM_000854]
A_23_P401568MAT2A1.7902563.71E-122.27E-102.27E-10UpHomo sapiens methionine adenosyltransferase II, alpha (MAT2A), mRNA [NM_005911]
A_23_P136978SRPX21.873334E-122.44E-102.44E-10UpHomo sapiens sushi-repeat-containing protein, X-linked 2 (SRPX2), mRNA [NM_014467]
A_23_P162068SLC1A22.6286324.91E-122.94E-102.94E-10UpHomo sapiens solute carrier family 1 (glial high affinity glutamate transporter), member 2 (SLC1A2), mRNA [NM_004171]
A_23_P364544C12ORF601.3787075.25E-123.11E-103.11E-10UpChromosome 12 open reading frame 60
A_23_P161616THC20240731.356355.76E-123.39E-103.39E-10UpFRA1_HUMAN (P15407) Fos-related antigen 1 (FRA-1), complete [THC2024073]
A_23_P123336PPM2C1.441166.53E-123.77E-103.77E-10UpHomo sapiens protein phosphatase 2C, magnesium-depend- ent, catalytic subunit (PPM2C), nuclear gene encoding mitochondrial protein, mRNA [NM_018444]
A_23_P338919APEG12.2068897.04E-124.04E-104.04E-10UpHomo sapiens aortic preferentially expressed protein 1 (APEG1), mRNA [NM_005876]
A_23_P36658MGST11.6050837.37E-124.2E-104.2E-10UpHomo sapiens microsomal glutathione S-transferase 1 (MGST1), transcript variant 1c, mRNA [NM_145791]
A_23_P102364NGEF3.0662588.01E-124.54E-104.54E-10UpHomo sapiens neuronal guanine nucleotide exchange factor (NGEF), mRNA [NM_019850]
A_23_P159328ANGPTL42.4075778.2E-124.61E-104.61E-10UpHomo sapiens angiopoietin-like 4 (ANGPTL4), transcript variant 2, mRNA [NM_016109]
A_23_P206212THBS11.5854918.41E-124.71E-104.71E-10UpHomo sapiens thrombospondin 1 (THBS1), mRNA [NM_003246]
A_23_P349966TMEM1301.8557698.65E-124.82E-104.82E-10UpTransmembrane protein 130
A_23_P91562C21orf251.972979.76E-125.39E-105.39E-10UpHomo sapiens chromosome 21 open reading frame 25 (C21orf25), mRNA [NM_199050]
A_23_P388220RALYL1.4135889.77E-125.39E-105.39E-10UpRALY RNA binding protein-like
A_23_P210274PREI33.0023671.08E-115.87E-105.87E-10UpHomo sapiens preimplantation protein 3 (PREI3), transcript variant 1, mRNA [NM_015387]
A_23_P314151NOLC11.3882531.09E-115.87E-105.87E-10UpHomo sapiens nucleolar and coiled-body phosphoprotein 1 (NOLC1), mRNA [NM_004741]
A_23_P131846SNAI11.6116081.1E-115.92E-105.92E-10UpHomo sapiens snail homolog 1 (Drosophila) (SNAI1), mRNA [NM_005985]
A_23_P63319SOAT11.8605161.13E-116.07E-106.07E-10UpHomo sapiens sterol O-acyltransferase (acyl-Coenzyme A: cholesterol acyltransferase) 1 (SOAT1), transcript variant 688113, mRNA [NM_003101]
A_23_P209360KBTBD91.9894051.23E-116.55E-106.55E-10UpHomo sapiens mRNA for KIAA1921 protein, partial cds. [AB067508]
A_23_P115726SLC16A93.1588421.38E-117.23E-107.23E-10UpHomo sapiens solute carrier family 16 (monocarbox- ylic acid transporters), member 9 (SLC16A9), mRNA [NM_194298]
A_23_P34478GIPC21.3657161.41E-117.35E-107.35E-10UpHomo sapiens PDZ domain protein GIPC2 (GIPC2), mRNA [NM_017655]
A_23_P404628G1P22.3060671.6E-118.25E-108.25E-10UpHomo sapiens interferon, alpha-inducible protein (clone IFI- 15K) (G1P2), mRNA [NM_005101]
A_23_P89431CCL23.2597441.79E-119.12E-109.12E-10UpHomo sapiens chemokine (C-C motif) ligand 2 (CCL2), mRNA [NM_002982]
A_23_P69280ALAS12.8750071.85E-119.38E-109.38E-10UpHomo sapiens aminolevulinate, delta-, synthase 1 (ALAS1), transcript variant 1, mRNA [NM_000688]
A_23_P357780FDX12.6197672.15E-111.08E-091.08E-09UpHomo sapiens ferredoxin 1 (FDX1), nuclear gene encoding mitochondrial protein, mRNA [NM_004109]
A_23_P205336C14orf1291.9976032.21E-111.11E-091.11E-09UpHomo sapiens cDNA FLJ20789 fis, clone COL01731. [AK000796]
Table 1 (continued)
Agiliant IdGene symbolLogFCP valueFDRT valueRegulationGene name
A_23_P87889DUSP161.3917552.4E-111.19E-091.19E-09UpHomo sapiens mRNA for KIAA1700 protein, partial cds. [AB051487]
A_23_P342727STARD131.5641652.79E-111.37E-091.37E-09UpHomo sapiens START domain containing 13 (STARD13), transcript variant gamma, mRNA [NM_052851]
A_23_P361514SNF1LK1.7198622.9E-111.41E-091.41E-09UpHomo sapiens mRNA for FLJ00263 protein. [AK131076]
A_23_P57836#N/A1.7005772.91E-111.41E-091.41E-09UpUnknown
A_23_P152876RAB341.9846463.14E-111.49E-091.49E-09UpHomo sapiens RAB34, member RAS oncogene family (RAB34), mRNA [NM_031934]
A_23_P3532LITAF1.3372063.38E-111.59E-091.59E-09UpHomo sapiens lipopolysaccharide-induced TNF factor (LITAF), mRNA [NM_004862]
A_23_P141636DDX481.3778143.47E-111.63E-091.63E-09UpHomo sapiens DEAD (Asp-Glu-Ala-Asp) box polypeptide 48 (DDX48), mRNA [NM_014740]
A_23_P207058SOCS32.2680493.72E-111.72E-091.72E-09UpHomo sapiens suppressor of cytokine signaling 3 (SOCS3), mRNA [NM_003955]
A_23_P166508BC0382451.6306963.88E-111.8E-091.8E-09UpHomo sapiens, clone IMAGE:5241654, mRNA. [BC038245]
A_23_P73480SGNE13.1730074.01E-111.85E-091.85E-09UpHomo sapiens secretory granule, neuroendocrine protein 1 (7B2 protein) (SGNE1), mRNA [NM_003020]
A_23_P142560ZFHX1B1.5108084.22E-111.94E-091.94E-09UpHomo sapiens zinc finger homeobox 1b (ZFHX1B), mRNA [NM_014795]
A_23_P62081SGNE12.7372544.68E-112.13E-092.13E-09UpHomo sapiens secretory granule, neuroendocrine protein 1 (7B2 protein) (SGNE1), mRNA [NM_003020]
A_23_P83220HSPA51.3795925.27E-112.37E-092.37E-09UpHomo sapiens heat shock 70 kDa protein 5 (glucose-regu- lated protein, 78 kDa) (HSPA5), mRNA [NM_005347]
A_23_P360232MT1X1.7945765.48E-112.45E-092.45E-09UpHomo sapiens metallothionein 1X (MT1X), mRNA [NM_005952]
A_23_P208591LDLR1.9666816.42E-112.82E-092.82E-09UpHomo sapiens low density lipoprotein receptor (familial hypercholesterolemia) (LDLR), mRNA [NM_000527]
A_23_P79398IL1R22.2831386.46E-112.83E-092.83E-09UpHomo sapiens interleukin 1 receptor, type II (IL1R2), tran- script variant 1, mRNA [NM_004633]
A_23_P211039ADAMTS12.045316.8E-112.94E-092.94E-09UpHomo sapiens a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 1 (ADAMTS1), mRNA [NM_006988]
A_23_P70670CD831.8650166.86E-112.96E-092.96E-09UpHomo sapiens CD83 antigen (activated B lympho- cytes, immunoglobulin superfamily) (CD83), mRNA [NM_004233]
A_23_P411296CEBPB1.5881127.01E-113E-093E-09UpHomo sapiens CCAAT/enhancer binding protein (C/EBP), beta (CEBPB), mRNA [NM_005194]
A_23_P126925SFPQ1.3494857.75E-113.24E-093.24E-09UpHomo sapiens splicing factor proline/glutamine rich (polypy- rimidine tract binding protein associated) (SFPQ), mRNA [NM_005066]
A_23_P56956TXNDC71.6132588.15E-113.38E-093.38E-09UpHomo sapiens thioredoxin domain containing 7 (protein disulfideisomerase) (TXNDC7), mRNA [NM_005742]
A_23_P15179MT1F1.8362528.63E-113.55E-093.55E-09UpHomo sapiens metallothionein 1F (functional) (MT1F), mRNA [NM_005949]
A_23_P357724KCNK32.1060299.52E-113.88E-093.88E-09UpHomo sapiens potassium channel, subfamily K, member 3 (KCNK3), mRNA [NM_002246]
A_23_P354704ST8SIA11.4081871.13E-104.54E-094.54E-09UpHomo sapiens sialyltransferase 8A (alpha-N-acetylneurami- nate: alpha-2,8-sialyltransferase, GD3 synthase) (SIAT8A), mRNA [NM_003034]
A_23_P144188SLC33A11.3826471.39E-105.45E-095.45E-09UpHomo sapiens solute carrier family 33 (acetyl-CoA trans- porter), member 1 (SLC33A1), mRNA [NM_004733]
A_23_P378430STARD63.4574451.42E-105.55E-095.55E-09UpHomo sapiens START domain containing 6 (STARD6), mRNA [NM_139171]
A_23_P429977KCNQ12.5155651.54E-105.95E-095.95E-09UpHomo sapiens potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1), transcript variant 1, mRNA [NM_000218]
A_23_P256470NPY2.4295661.67E-106.38E-096.38E-09UpHomo sapiens neuropeptide Y (NPY), mRNA [NM_000905]
A_23_P54840MT1A1.5189181.91E-107.28E-097.28E-09UpHomo sapiens metallothionein 1A (functional) (MT1A), mRNA [NM_005946]
A_23_P132121SNF1LK1.3687122.31E-108.61E-098.61E-09UpHomo sapiens SNF1-like kinase (SNF1LK), mRNA [NM_173354]
A_23_P150016DUSP51.4339342.65E-109.69E-099.69E-09UpHomo sapiens dual specificity phosphatase 5 (DUSP5), mRNA [NM_004419]
Table 1 (continued)
Agiliant IdGene symbolLogFCP valueFDRT valueRegulationGene name
A_23_P134125MAP3K51.6149552.81E-101.03E-081.03E-08UpHomo sapiens mitogen-activated protein kinase kinasekinase 5 (MAP3K5), mRNA [NM_005923]
A_23_P257478CYP21A22.199992.92E-101.06E-081.06E-08UpHomo sapiens cytochrome P450, family 21, subfamily A, polypeptide 2 (CYP21A2), mRNA [NM_000500]
A_23_P162616MGC353663.1112463.34E-101.19E-081.19E-08UpHomo sapiens hypothetical protein MGC35366 (MGC35366), mRNA [NM_152435]
A_23_P375906MAPK41.7873384.02E-101.4E-081.4E-08UpHomo sapiens mitogen-activated protein kinase 4 (MAPK4), mRNA [NM_002747]
A_23_P216167PSD32.0988874.05E-101.41E-081.41E-08UpHomo sapiens pleckstrin and Sec7 domain containing 3 (PSD3), transcript variant 1, mRNA [NM_015310]
A_23_P214108TPMT1.6104754.8E-101.65E-081.65E-08UpHomo sapiens thiopurine S-methyltransferase (TPMT), mRNA [NM_000367]
A_23_P378416GPM6B1.9238345.85E-101.96E-081.96E-08UpHomo sapiens glycoprotein M6B (GPM6B), transcript vari- ant 3, mRNA [NM_005278]
A_23_P154037AOX12.3060456.16E-102.05E-082.05E-08UpHomo sapiens aldehyde oxidase 1 (AOX1), mRNA [NM_001159]
A_23_P155596FMO32.0472636.94E-102.28E-082.28E-08UpHomo sapiens flavin-containing monooxygenase 3 (FMO3), transcript variant 1, mRNA [NM_006894]
A_23_P138168CNN31.3715126.99E-102.29E-082.29E-08UpHomo sapiens calponin 3, acidic (CNN3), mRNA [NM_001839]
A_23_P216335THC20500171.3591857.5E-102.43E-082.43E-08UpQ9SS92 (Q9SS92) F4P13.17 protein, partial (3%) [THC2050017]
A_23_P75358CTSD1.3378727.96E-102.56E-082.56E-08UpHomo sapiens cDNA FLJ12231 fis, clone MAMMA1001191. [AK022293]
A_23_P106611WFDC11.6433678.91E-102.8E-082.8E-08UpHomo sapiens WAP four-disulfide core domain 1 (WFDC1), mRNA [NM_021197]
A_23_P120644HIGD1AP161.494799.06E-102.84E-082.84E-08UpHIG1 hypoxia-inducible domain family member 1A pseu- dogene 16
A_23_P6344SDF2L11.4214769.38E-102.92E-082.92E-08UpHomo sapiens stromal cell-derived factor 2-like 1 (SDF2L1), mRNA [NM_022044]
A_23_P163782MT1H1.7619431.01E-093.09E-083.09E-08UpHomo sapiens metallothionein 1H (MT1H), mRNA [NM_005951]
A_23_P300033PDGFRA2.5057071.11E-093.35E-083.35E-08UpHomo sapiens platelet-derived growth factor receptor, alpha polypeptide (PDGFRA), mRNA [NM_006206]
A_23_P21485PID11.5956161.11E-093.35E-083.35E-08UpPhosphotyrosine interaction domain containing 1
A_23_P129695VASN2.2043151.12E-093.37E-083.37E-08Upvasorin
A_23_P203115TMEM251.5727611.18E-093.52E-083.52E-08UpHomo sapiens transmembrane protein 25 (TMEM25), mRNA [NM_032780]
A_23_P142849RND32.0229941.21E-093.61E-083.61E-08UpHomo sapiens Rho family GTPase 3 (RND3), mRNA [NM_005168]
A_23_P42575CALD11.4372941.23E-093.66E-083.66E-08UpHomo sapiens caldesmon 1 (CALD1), transcript variant 4, mRNA [NM_033139]
A_23_P107356NALP12.0399841.26E-093.72E-083.72E-08UpHomo sapiens NACHT, leucine-rich repeat and PYD (pyrin domain) containing 1, mRNA (cDNA clone MGC:57544 IMAGE:5756099), complete cds. [BC051787]
A_23_P303242MT1X1.8280411.26E-093.74E-083.74E-08UpHomo sapiens metallothionein 1X (MT1X), mRNA [NM_005952]
A_23_P414343MT1J1.6605211.47E-094.26E-084.26E-08UpHomo sapiens metallothionein 1J (MT1J), mRNA [NM_175622]
A_23_P8754AASS1.3429991.48E-094.28E-084.28E-08UpHomo sapiens aminoadipate-semialdehyde synthase (AASS), mRNA [NM_005763]
A_23_P208101MAPK42.9770191.51E-094.36E-084.36E-08UpMitogen-activated protein kinase 4 (EC 2.7.1.37) (Extra- cellular signal-regulated kinase 4) (ERK-4) (MAP kinase isoform p63) (p63- MAPK). [Source: Uniprot/ SWISSPROT;Acc:P31152] [ENST00000269463]
A_23_P40885HIG11.4945171.65E-094.7E-084.7E-08UpHomo sapiens likely ortholog of mouse hypoxia induced gene 1 (HIG1), mRNA [NM_014056]
A_23_P81770PTP4A12.4600921.72E-094.87E-084.87E-08UpHomo sapiens protein tyrosine phosphatase type IVA, mem- ber 1 (PTP4A1), mRNA [NM_003463]
A_23_P56197CRLF12.1219832.26E-096.22E-086.22E-08UpHomo sapiens cytokine receptor-like factor 1 (CRLF1), mRNA [NM_004750]
Table 1 (continued)
Agiliant IdGene symbolLogFCP valueFDRT valueRegulationGene name
A_23_P391906KIAA19131.8657722.38E-096.49E-086.49E-08UpHomo sapiens KIAA1913, mRNA (cDNA clone MGC:50847 IMAGE:5760073), complete cds. [BC044246]
A_23_P3261PDE8A1.5496952.57E-096.91E-086.91E-08UpHomo sapiens phosphodiesterase 8A (PDE8A), transcript variant 5, mRNA [NM_173457]
A_23_P26037FRMD51.9610812.62E-097.02E-087.02E-08UpFERM domain containing 5
A_23_P4821JUNB1.3574553.31E-098.61E-088.61E-08UpHomo sapiens jun B proto-oncogene (JUNB), mRNA [NM_002229]
A_23_P156708TNXB2.2217483.54E-099.17E-089.17E-08UpHomo sapiens tenascin XB (TNXB), transcript variant XB, mRNA [NM_019105]
A_23_P126706ANGPTL11.9743093.55E-099.19E-089.19E-08UpHomo sapiens angiopoietin-like 1 (ANGPTL1), mRNA [NM_004673]
A_23_P121795ARGBP22.0990973.63E-099.35E-089.35E-08UpHomo sapiens Arg/Abl-interacting protein ArgBP2 (ARGBP2), transcript variant 2, mRNA [NM_021069]
A_23_P98375FDX12.5117543.75E-099.67E-089.67E-08UpHomo sapiens ferredoxin 1 (FDX1), nuclear gene encoding mitochondrial protein, mRNA [NM_004109]
A_23_P94333ENPP21.5092633.84E-099.84E-089.84E-08UpHomo sapiens ectonucleotidepyrophosphatase/phosphodies- terase 2 (autotaxin) (ENPP2), mRNA [NM_006209]
A_23_P20573THC20845583.5444643.93E-091E-071E-07UpBC029647 RUSC2 protein {Homo sapiens; }, partial (40%) [THC2084558]
A_23_P14621FGF71.7360634.4E-091.11E-071.11E-07UpHomo sapiens fibroblast growth factor 7 (keratinocyte growth factor) (FGF7), mRNA [NM_002009]
A_23_P379481DHCR241.6567984.41E-091.11E-071.11E-07UpHomo sapiens 24-dehydrocholesterol reductase (DHCR24), mRNA [NM_014762]
A_23_P50946RAMP11.62984.95E-091.23E-071.23E-07UpHomo sapiens receptor (calcitonin) activity modifying protein 1 (RAMP1), mRNA [NM_005855]
A_23_P38732CDH22.0172344.99E-091.24E-071.24E-07UpHomo sapiens cadherin 2, type 1, N-cadherin (neuronal) (CDH2), mRNA [NM_001792]
A_23_P167920DLL11.3545225.15E-091.27E-071.27E-07UpHomo sapiens delta-like 1 (Drosophila) (DLL1), mRNA [NM_005618]
A_23_P38735CDH192.2455465.27E-091.3E-071.3E-07UpHomo sapiens cadherin 19, type 2 (CDH19), mRNA [NM_021153]
A_23_P348737NR2F11.8837525.4E-091.33E-071.33E-07UpHomo sapiens nuclear receptor subfamily 2, group F, mem- ber 1 (NR2F1), mRNA [NM_005654]
A_23_P151506PLEK21.4251055.46E-091.34E-071.34E-07UpHomo sapiens pleckstrin 2 (PLEK2), mRNA [NM_016445]
A_23_P162047DKK31.8023465.54E-091.36E-071.36E-07UpHomo sapiens dickkopf homolog 3 (Xenopuslaevis) (DKK3), mRNA [NM_013253]
A_23_P56630STAT11.7346795.93E-091.45E-071.45E-07UpHomo sapiens signal transducer and activator of transcrip- tion 1, 91 kDa (STAT1), transcript variant alpha, mRNA [NM_007315]
A_23_P161647PC1.5261316.67E-091.59E-071.59E-07UpHomo sapiens pyruvate carboxylase (PC), nuclear gene encoding mitochondrial protein, transcript variant A, mRNA [NM_000920]
A_23_P32253NFIL31.8903357.12E-091.68E-071.68E-07UpHomo sapiens nuclear factor, interleukin 3 regulated (NFIL3), mRNA [NM_005384]
A_23_P6674LXN1.801667.33E-091.73E-071.73E-07UpHomo sapiens latexin (LXN), mRNA [NM_020169]
A_23_P65278NBEA1.3539147.61E-091.79E-071.79E-07UpHomo sapiens neurobeachin (NBEA), mRNA [NM_015678]
A_23_P169189IKBKAP1.4202728.03E-091.87E-071.87E-07UpHomo sapiens inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase complex-associated protein (IKBKAP), mRNA [NM_003640]
A_23_P416581GNAZ1.9487999.12E-092.06E-072.06E-07UpHomo sapiens guanine nucleotide binding protein (G pro- tein), alpha z polypeptide (GNAZ), mRNA [NM_002073]
A_23_P111689THC21247281.6663039.76E-092.19E-072.19E-07UpPBEF_HUMAN (P43490) Pre-B cell enhancing factor precursor, partial (16%) [THC2124728]
A_23_P75111CYP17A12.4597449.99E-092.22E-072.22E-07UpHomo sapiens cytochrome P450, family 17, subfamily A, polypeptide 1 (CYP17A1), mRNA [NM_000102]
A_23_P374862DAF1.3373541.02E-082.26E-072.26E-07UpHomo sapiens decay accelerating factor for complement (CD55, Cromer blood group system) (DAF), mRNA [NM_000574]
A_23_P24903P2RY21.6271551.03E-082.28E-072.28E-07UpHomo sapiens purinergic receptor P2Y, G protein-coupled, 2 (P2RY2), transcript variant 1, mRNA [NM_176072]
A_23_P25964GALC1.5080071.04E-082.31E-072.31E-07UpHomo sapiens galactosylceramidase (Krabbe disease) (GALC), mRNA [NM_000153]
Table 1 (continued)
Agiliant IdGene symbolLogFCP valueFDRT valueRegulationGene name
A_23_P144369NAP1L52.0768341.36E-082.92E-072.92E-07UpHomo sapiens nucleosome assembly protein 1-like 5 (NAP1L5), mRNA [NM_153757]
A_23_P97265GPATC41.3985741.39E-082.98E-072.98E-07UpHomo sapiens G patch domain containing 4 (GPATC4), transcript variant 1, mRNA [NM_015590]
A_23_P164654APOE2.3178981.52E-083.22E-073.22E-07UpHomo sapiens apolipoprotein E (APOE), mRNA [NM_000041]
A_23_P305060PBEF12.2732751.58E-083.31E-073.31E-07UpHomo sapiens pre-B-cell colony enhancing factor 1 (PBEF1), transcript variant 1, mRNA [NM_005746]
A_23_P94319KIAA07111.7272651.59E-083.33E-073.33E-07UpHomo sapiens KIAA0711 gene product (KIAA0711), mRNA [NM_014867]
A_23_P7451AF0879782.0344591.63E-083.4E-073.4E-07UpHomo sapiens full-length insert cDNA clone YW26E10. [AF087978]
A_23_P123234#N/A1.37441.7E-083.54E-073.54E-07UpUnknown
A_23_P127948ADM2.0003681.8E-083.73E-073.73E-07UpHomo sapiens adrenomedullin (ADM), mRNA [NM_001124]
A_23_P153320ICAM11.3748331.92E-083.95E-073.95E-07UpHomo sapiens intercellular adhesion molecule 1 (CD54), human rhinovirus receptor (ICAM1), mRNA [NM_000201]
A_23_P12884GRK51.6124152.36E-084.69E-074.69E-07UpHomo sapiens G protein-coupled receptor kinase 5 (GRK5), mRNA [NM_005308]
A_23_P108574PRKD31.7285242.62E-085.14E-075.14E-07UpHomo sapiens protein kinase D3 (PRKD3), mRNA [NM_005813]
A_23_P119562DF2.1165952.86E-085.56E-075.56E-07UpHomo sapiens D component of complement (adipsin) (DF), mRNA [NM_001928]
A_23_P60933MT1G1.806283.61E-086.83E-076.83E-07UpHomo sapiens metallothionein 1G (MT1G), mRNA [NM_005950]
A_23_P120845XBP11.5042173.93E-087.31E-077.31E-07UpHomo sapiens X-box binding protein 1 (XBP1), mRNA [NM_005080]
A_23_P31810CEBPD1.5125574.54E-088.35E-078.35E-07UpHomo sapiens CCAAT/enhancer binding protein (C/EBP), delta (CEBPD), mRNA [NM_005195]
A_23_P91802ECGF11.4452314.58E-088.38E-078.38E-07UpHomo sapiens endothelial cell growth factor 1 (platelet- derived) (ECGF1), mRNA [NM_001953]
A_23_P82245ENST000003287421.7158014.95E-088.98E-078.98E-07UpUnknown
A_23_P143143ID21.5434815.7E-081.02E-061.02E-06UpHomo sapiens inhibitor of DNA binding 2, dominant nega- tive helix-loop-helix protein (ID2), mRNA [NM_002166]
A_23_P82868PLAT2.0312626.26E-081.1E-061.1E-06UpHomo sapiens plasminogen activator, tissue (PLAT), tran- script variant 1, mRNA [NM_000930]
A_23_P12643AS3MT2.5691426.42E-081.13E-061.13E-06UpHomo sapiens arsenic (+3 oxidation state) methyltransferase (AS3MT), mRNA [NM_020682]
A_23_P5365RPRM2.3930046.72E-081.18E-061.18E-06UpHomo sapiens reprimo, TP53 dependant G2 arrest mediator candidate (RPRM), mRNA [NM_019845]
A_23_P26965CCL131.7540466.9E-081.2E-061.2E-06UpHomo sapiens chemokine (C-C motif) ligand 13 (CCL13), mRNA [NM_005408]
A_23_P132956UCHL12.236846.9E-081.2E-061.2E-06UpHomo sapiens ubiquitin carboxyl-terminal esterase L1 (ubiq- uitin thiolesterase) (UCHL1), mRNA [NM_004181]
A_23_P151805FBLN51.4873347.21E-081.25E-061.25E-06UpHomo sapiens fibulin 5 (FBLN5), mRNA [NM_006329]
A_23_P103951#N/A1.4049917.62E-081.3E-061.3E-06UpUnknown
A_23_P257087PDK41.5897067.86E-081.34E-061.34E-06UpHomo sapiens pyruvate dehydrogenase kinase, isoenzyme 4 (PDK4), mRNA [NM_002612]
A_23_P128230NR4A11.8533789.07E-081.51E-061.51E-06UpHomo sapiens nuclear receptor subfamily 4, group A, mem- ber 1 (NR4A1), transcript variant 1, mRNA [NM_002135]
A_23_P65558MGAT21.6355839.13E-081.52E-061.52E-06UpHomo sapiens mannosyl (alpha-1,6-)-glycoprotein beta-1,2-N-acetylglucosaminyltransferase (MGAT2), mRNA [NM_002408]
A_23_P37983MT1B1.8419459.28E-081.54E-061.54E-06UpHomo sapiens metallothionein 1B (functional) (MT1B), mRNA [NM_005947]
A_23_P258190AKR1B11.8403379.58E-081.58E-061.58E-06UpHomo sapiens aldo-ketoreductase family 1, member B1 (aldose reductase) (AKR1B1), mRNA [NM_001628]
A_23_P213184ADH1B2.3865739.7E-081.6E-061.6E-06UpHomo sapiens alcohol dehydrogenase IB (class I), beta polypeptide (ADH1B), mRNA [NM_000668]
A_23_P2831EDNRB1.4485519.72E-081.6E-061.6E-06UpHomo sapiens endothelin receptor type B (EDNRB), tran- script variant 2, mRNA [NM_003991]
Table 1 (continued)
Agiliant IdGene symbolLogFCP valueFDRT valueRegulationGene name
A_23_P16915QPCT2.3719311.03E-071.68E-061.68E-06UpHomo sapiens glutaminyl-peptide cyclotransferase (glutami- nylcyclase) (QPCT), mRNA [NM_012413]
A_23_P146274STMN22.1808351.25E-072.01E-062.01E-06UpHomo sapiens stathmin-like 2 (STMN2), mRNA [NM_007029]
A_23_P363936HSPA4L1.5285261.52E-072.39E-062.39E-06UpHomo sapiens heat shock 70 kDa protein 4-like (HSPA4L), mRNA [NM_014278]
A_23_P102331SCN7A1.3500161.53E-072.4E-062.4E-06UpQ16278 (Q16278) Voltage-dependent sodium channel alpha subunit protein (Fragment), partial (18%) [THC2123516]
A_23_P33723CD1631.5100971.78E-072.72E-062.72E-06UpHomo sapiens CD163 antigen (CD163), transcript variant 1, mRNA [NM_004244]
A_23_P206701MT1G1.986971.81E-072.77E-062.77E-06UpHomo sapiens metallothionein 1G (MT1G), mRNA [NM_005950]
A_23_P144274MARLIN11.6639051.84E-072.8E-062.8E-06UpHomo sapiens multiple coiled-coil GABABR1-binding protein (MARLIN1), mRNA [NM_144720]
A_23_P13609PBP1.4212021.85E-072.82E-062.82E-06UpHomo sapiens prostatic binding protein (PBP), mRNA [NM_002567]
A_23_P86470CH25H1.578691.86E-072.83E-062.83E-06UpHomo sapiens cholesterol 25-hydroxylase (CH25H), mRNA [NM_003956]
A_23_P70968HOXA71.3807631.92E-072.9E-062.9E-06UpHomo sapiens homeo box A7 (HOXA7), mRNA [NM_006896]
A_23_P82526ABCB12.8950771.96E-072.96E-062.96E-06UpHomo sapiens ATP-binding cassette, subfamily B (MDR/ TAP), member 1 (ABCB1), mRNA [NM_000927]
A_23_P165418BZW11.5545342.1E-073.14E-063.14E-06UpHomo sapiens basic leucine zipper and W2 domains 1 (BZW1), mRNA [NM_014670]
A_23_P18078RARRES12.6105132.22E-073.3E-063.3E-06UpHomo sapiens retinoic acid receptor responder (tazarotene induced) 1 (RARRES1), transcript variant 2, mRNA [NM_002888]
A_23_P71290YWHAZ1.3646312.4E-073.52E-063.52E-06UpHomo sapiens tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide (YWHAZ), transcript variant 2, mRNA [NM_145690]
A_23_P259442CPE1.7606122.42E-073.55E-063.55E-06UpHomo sapiens carboxypeptidase E (CPE), mRNA [NM_001873]
A_23_P83098ALDH1A11.8469952.73E-073.94E-063.94E-06UpHomo sapiens aldehyde dehydrogenase 1 family, member A1 (ALDH1A1), mRNA [NM_000689]
A_23_P434809S100A82.5948442.92E-074.18E-064.18E-06UpHomo sapiens S100 calcium binding protein A8 (calgranulin A) (S100A8), mRNA [NM_002964]
A_23_P82121ARHGAP181.3649243.25E-074.59E-064.59E-06UpHomo sapiens Rho GTPase activating protein 18 (ARH- GAP18), mRNA [NM_033515]
A_23_P37484CHSY11.657273.32E-074.67E-064.67E-06UpHomo sapiens carbohydrate (chondroitin) synthase 1 (CHSY1), mRNA [NM_014918]
A_23_P154806EPB41L11.4138393.48E-074.86E-064.86E-06UpHomo sapiens erythrocyte membrane protein band 4.1-like 1 (EPB41L1), transcript variant 1, mRNA [NM_012156]
A_23_P47725MAP61.4340584.09E-075.58E-065.58E-06UpHomo sapiens microtubule-associated protein 6 (MAP6), transcript variant 1, mRNA [NM_033063]
A_23_P149322LOC559241.5162914.11E-075.6E-065.6E-06UpHomo sapiens hypothetical protein LOC55924 (LOC55924), transcript variant 1, mRNA [NM_019099]
A_23_P200288S100A82.2756844.22E-075.72E-065.72E-06UpHomo sapiens S100 calcium binding protein A8 (calgranulin A) (S100A8), mRNA [NM_002964]
A_23_P105803FGF91.6511034.42E-075.95E-065.95E-06UpHomo sapiens fibroblast growth factor 9 (glia-activating fac- tor) (FGF9), mRNA [NM_002010]
A_23_P112281TMOD11.3969584.46E-075.99E-065.99E-06UpHomo sapiens tropomodulin 1 (TMOD1), mRNA [NM_003275]
A_23_P259156RGN1.7174324.65E-076.22E-066.22E-06UpHomo sapiens regucalcin (senescence marker protein-30) (RGN), transcript variant 1, mRNA [NM_004683]
A_23_P72968ARHGAP363.0283725.03E-076.65E-066.65E-06UpRho GTPase activating protein 36
A_23_P71037IL61.8519615.17E-076.8E-066.8E-06UpHomo sapiens interleukin 6 (interferon, beta 2) (IL6), mRNA [NM_000600]
A_23_P211727FGF122.1697965.21E-076.84E-066.84E-06UpHomo sapiens fibroblast growth factor 12 (FGF12), transcript variant 2, mRNA [NM_004113]
A_23_P93591GJA11.4258885.31E-076.95E-066.95E-06UpHomo sapiens gap junction protein, alpha 1, 43 kDa (con- nexin 43) (GJA1), mRNA [NM_000165]
A_23_P42414NEDD91.5646256.92E-078.75E-068.75E-06UpHomo sapiens neural precursor cell expressed, developmen- tally down-regulated 9 (NEDD9), mRNA [NM_006403]
Table 1 (continued)
Agiliant IdGene symbolLogFCP valueFDRT valueRegulationGene name
A_23_P111402THSD21.9028686.95E-078.79E-068.79E-06UpHomo sapiens thrombospondin, type I, domain containing 2 (THSD2), mRNA [NM_032784]
A_23_P81158ADH1C1.9780767.04E-078.88E-068.88E-06UpHomo sapiens alcohol dehydrogenase 1C (class I), gamma polypeptide (ADH1C), mRNA [NM_000669]
A_23_P124598SLCO2A11.4066799.47E-071.15E-051.15E-05UpHomo sapiens solute carrier organic anion transporter family, member 2A1 (SLCO2A1), mRNA [NM_005630]
A_23_P503182ABR1.5636869.91E-071.19E-051.19E-05UpHomo sapiens active BCR-related gene (ABR), transcript variant 1, mRNA [NM_021962]
A_23_P211631FBLN11.9940651.04E-061.24E-051.24E-05UpHomo sapiens fibulin 1 (FBLN1), transcript variant D, mRNA [NM_006486]
A_23_P161559RAB381.5651421.06E-061.27E-051.27E-05UpHomo sapiens RAB38, member RAS oncogene family (RAB38), mRNA [NM_022337]
A_23_P87013TAGLN1.4331931.09E-061.3E-051.3E-05UpHomo sapiens transgelin (TAGLN), transcript variant 2, mRNA [NM_003186]
A_23_P52336UNC5B1.4010671.1E-061.31E-051.31E-05UpHomo sapiens unc-5 homolog B (C. elegans) (UNC5B), mRNA [NM_170744]
A_23_P203558HBB2.3261881.12E-061.33E-051.33E-05UpHomo sapiens hemoglobin, beta (HBB), mRNA [NM_000518]
A_23_P64873DCN2.3594461.31E-061.51E-051.51E-05UpHomo sapiens decorin (DCN), transcript variant A1, mRNA [NM_001920]
A_23_P6321CLDN51.3707151.6E-061.79E-051.79E-05UpHomo sapiens claudin 5 (transmembrane protein deleted in velocardiofacial syndrome) (CLDN5), mRNA [NM_003277]
A_23_P111132HSPA1A1.7165851.64E-061.83E-051.83E-05UpHomo sapiens heat shock 70 kDa protein 1A (HSPA1A), mRNA [NM_005345]
A_23_P500998HOXA91.4333171.8E-061.98E-051.98E-05UpHomo sapiens homeo box A9 (HOXA9), transcript variant 1, mRNA [NM_152739]
A_23_P4649APOC12.1438011.92E-062.09E-052.09E-05UpHomo sapiens apolipoprotein C-I (APOC1), mRNA [NM_001645]
A_23_P417974AQP111.784821.94E-062.11E-052.11E-05UpHomo sapiens aquaporin 11 (AQP11), mRNA [NM_173039]
A_23_P304450GATA61.6684942.13E-062.28E-052.28E-05UpHomo sapiens GATA binding protein 6 (GATA6), mRNA [NM_005257]
A_23_P17998HES11.3633442.14E-062.28E-052.28E-05UpHomo sapiens hairy and enhancer of split 1, (Drosophila) (HES1), mRNA [NM_005524]
A_23_P103996GCLM2.0838872.41E-062.53E-052.53E-05UpHomo sapiens glutamate-cysteine ligase, modifier subunit (GCLM), mRNA [NM_002061]
A_23_P206724MT1E1.806272.64E-062.76E-052.76E-05UpHomo sapiens metallothionein 1E (functional) (MT1E), mRNA [NM_175617]
A_23_P99515MEDAG1.4095063.19E-063.23E-053.23E-05Upmesenteric estrogen dependent adipogenesis
A_23_P60776PSPHL3.1273693.2E-063.23E-053.23E-05UpHomo sapiens phosphoserine phosphatase-like, mRNA (cDNA clone IMAGE:5552627), partial cds. [BC065228]
A_23_P202448CXCL121.8997383.44E-063.44E-053.44E-05UpHomo sapiens chemokine (C-X-C motif) ligand 12 (stromal cell-derived factor 1) (CXCL12), mRNA [NM_199168]
A_23_P347632MTSS11.3588823.45E-063.45E-053.45E-05UpHomo sapiens metastasis suppressor 1 (MTSS1), mRNA [NM_014751]
A_23_P45536MCF21.4463033.76E-063.73E-053.73E-05UpHomo sapiens MCF.2 cell line derived transforming sequence (MCF2), mRNA [NM_005369]
A_23_P160286PRG42.3775183.95E-063.88E-053.88E-05UpHomo sapiens proteoglycan 4 (PRG4), mRNA [NM_005807]
A_23_P143845TIPARP1.3714174.31E-064.19E-054.19E-05UpHomo sapiens TCDD-inducible poly(ADP-ribose) polymer- ase (TIPARP), mRNA [NM_015508]
A_23_P258132DKFZp564I19221.6176965.1E-064.86E-054.86E-05UpHomo sapiens adlican (DKFZp564I1922), mRNA [NM_015419]
A_23_P205959ALDH1A31.4211675.67E-065.31E-055.31E-05UpHomo sapiens aldehyde dehydrogenase 1 family, member A3 (ALDH1A3), mRNA [NM_000693]
A_23_P58359ADH1A1.5324615.74E-065.37E-055.37E-05UpHomo sapiens alcohol dehydrogenase 1A (class I), alpha polypeptide (ADH1A), mRNA [NM_000667]
A_23_P164170PRKAR1A1.3867065.82E-065.43E-055.43E-05UpHomo sapiens protein kinase, cAMP-dependent, regulatory, type I, alpha (tissue specific extinguisher 1) (PRKAR1A), transcript variant 1, mRNA [NM_002734]
A_23_P426305AOC31.7792586.3E-065.82E-055.82E-05UpHomo sapiens amine oxidase, copper containing 3 (vascular adhesion protein 1) (AOC3), mRNA [NM_003734]
Table 1 (continued)
Agiliant IdGene symbolLogFCP valueFDRT valueRegulationGene name
A_23_P163306CGNL11.4169717.15E-066.51E-056.51E-05UpHomo sapiens cingulin-like 1 (CGNL1), mRNA [NM_032866]
A_23_P74609G0S21.5419317.19E-066.54E-056.54E-05UpHomo sapiens putative lymphocyte G0/G1 switch gene (G0S2), mRNA [NM_015714]
A_23_P139114SERPING11.4446387.31E-066.61E-056.61E-05UpHomo sapiens serine (or cysteine) proteinase inhibitor, clade G (C1 inhibitor), member 1, (angioedema, hereditary) (SERPING1), mRNA [NM_000062]
A_23_P257043GEM1.554888.51E-067.53E-057.53E-05UpHomo sapiens GTP binding protein overexpressed in skeletal muscle (GEM), transcript variant 1, mRNA [NM_005261]
A_23_P146134MGC11361.4991559.78E-068.46E-058.46E-05UpHomo sapiens hypothetical protein MGC1136 (MGC1136), mRNA [NM_024025]
A_23_P48513IFI271.4765511.17E-059.88E-059.88E-05UpHomo sapiens interferon, alpha-inducible protein 27 (IFI27), transcript variant a, mRNA [NM_005532]
A_23_P60802ADRA2C1.5176171.47E-050.0001210.000121UpHomo sapiens adrenergic, alpha-2C-, receptor (ADRA2C), mRNA [NM_000683]
A_23_P212905CXCL11.6500661.58E-050.0001290.000129UpHomo sapiens chemokine (C-X-C motif) ligand 1 (melanoma growth stimulating activity, alpha) (CXCL1), mRNA [NM_001511]
A_23_P82929NOV2.6115171.58E-050.0001290.000129UpHomo sapiens nephroblastoma overexpressed gene (NOV), mRNA [NM_002514]
A_23_P400449KIAA15761.7853861.73E-050.0001390.000139UpHomo sapiens KIAA1576 protein (KIAA1576), mRNA [NM_020927]
A_23_P257231AGXT2L11.6682581.78E-050.0001420.000142UpHomo sapiens alanine-glyoxylate aminotransferase 2-like 1 (AGXT2L1), mRNA [NM_031279]
A_23_P254102PI161.7725251.99E-050.0001560.000156UpHomo sapiens protease inhibitor 16 (PI16), mRNA [NM_153370]
A_23_P7752SEMA6A1.4993012.05E-050.0001610.000161UpHomo sapiens sema domain, transmembrane domain (TM), and cytoplasmic domain, (semaphorin) 6A (SEMA6A), mRNA [NM_020796]
A_23_P35995ASAM1.3547712.12E-050.0001650.000165UpHomo sapiens adipocyte-specific adhesion molecule (ASAM), mRNA [NM_024769]
A_23_P114883FMOD1.7539932.14E-050.0001660.000166UpHomo sapiens fibromodulin (FMOD), mRNA [NM_002023]
A_23_P125233CNN11.5316082.22E-050.0001710.000171UpHomo sapiens calponin 1, basic, smooth muscle (CNN1), mRNA [NM_001299]
A_23_P362148DNER1.6354142.27E-050.0001750.000175UpHomo sapiens delta-notch-like EGF repeat-containing trans- membrane (DNER), mRNA [NM_139072]
A_23_P23044S100A91.9226572.56E-050.0001930.000193UpHomo sapiens S100 calcium binding protein A9 (calgranulin B) (S100A9), mRNA [NM_002965]
A_23_P127033ECHDC31.5780452.73E-050.0002040.000204UpHomo sapiens enoyl Coenzyme A hydratase domain contain- ing 3 (ECHDC3), mRNA [NM_024693]
A_23_P82499PEG102.0288632.88E-050.0002130.000213UpHomo sapiens MEF3L1 mRNA for MEF3 like 1, complete cds. [AB049150]
A_23_P62807CGI-491.378773.14E-050.000230.00023UpHomo sapiens CGI-49 protein (CGI-49), mRNA [NM_016002]
A_23_P20392PSD31.4874713.24E-050.0002360.000236UpHomo sapiens pleckstrin and Sec7 domain containing 3, mRNA (cDNA clone IMAGE:4153308), complete cds. [BC011238]
A_23_P119642ATP4A2.1820964.71E-050.0003240.000324UpHomo sapiens ATPase, H+/K +exchanging, alpha polypep- tide (ATP4A), mRNA [NM_000704]
A_23_P41789SLC27A61.6237054.71E-050.0003240.000324UpHomo sapiens solute carrier family 27 (fatty acid trans- porter), member 6 (SLC27A6), mRNA [NM_014031]
A_23_P104492PAPSS21.5849935.07E-050.0003450.000345UpHomo sapiens 3'-phosphoadenosine 5'-phosphosulfate synthase 2 (PAPSS2), mRNA [NM_004670]
A_23_P147404#N/A1.4954525.14E-050.0003490.000349UpUnknown
A_23_P430728ATP4A2.1244775.44E-050.0003670.000367UpHomo sapiens ATPase, H+/K +exchanging, alpha polypep- tide (ATP4A), mRNA [NM_000704]
A_23_P92983BHMT21.3520675.46E-050.0003680.000368UpHomo sapiens betaine-homocysteinemethyltransferase 2 (BHMT2), mRNA [NM_017614]
A_23_P300600NEFH1.5144335.66E-050.0003790.000379UpHomo sapiens neurofilament, heavy polypeptide 200 kDa (NEFH), mRNA [NM_021076]
A_23_P214080EGR11.5012317.23E-050.0004640.000464UpHomo sapiens early growth response 1 (EGR1), mRNA [NM_001964]
Table 1 (continued)
Agiliant IdGene symbolLogFCP valueFDRT valueRegulationGene name
A_23_P16523GDF152.3381689.47E-050.0005860.000586UpHomo sapiens growth differentiation factor 15 (GDF15), mRNA [NM_004864]
A_23_P22526HEPH1.3445650.0001210.0007210.000721UpHomo sapiens hephaestin (HEPH), transcript variant 2, mRNA [NM_014799]
A_23_P643THC21607351.4874810.0001230.000730.00073UpQ8BIY2 (Q8BIY2) Musmusculus 10 days lacta- tion, adult female mammary gland cDNA, RIKEN full-length enriched library, clone: D730020K15 product:HRIHFB2003 PROTEIN homolog, partial (31%) [THC2160735]
A_23_P121533SPON21.7432320.0001260.0007480.000748UpHomo sapiens spondin 2, extracellular matrix protein (SPON2), mRNA [NM_012445]
A_23_P383819TBX31.3658740.000130.0007680.000768UpHomo sapiens T-box 3 (ulnar mammary syndrome) (TBX3), transcript variant 2, mRNA [NM_016569]
A_23_P408249PCK11.9347730.0001450.0008440.000844UpHomo sapiens phosphoenolpyruvatecarboxykinase 1 (solu- ble) (PCK1), mRNA [NM_002591]
A_23_P134237RARRES21.8945540.000150.0008690.000869UpHomo sapiens retinoic acid receptor responder (tazarotene induced) 2 (RARRES2), mRNA [NM_002889]
A_23_P42975PRKAR2B1.3733550.0001510.0008720.000872UpHomo sapiens protein kinase, cAMP-dependent, regulatory, type II, beta (PRKAR2B), mRNA [NM_002736]
A_23_P501007EFEMP11.5988320.0001830.0010270.001027UpHomo sapiens EGF-containing fibulin-like extracellular matrix protein 1 (EFEMP1), transcript variant 1, mRNA [NM_004105]
A_23_P119943IGFBP21.3732260.0002030.0011240.001124UpHomo sapiens insulin-like growth factor binding protein 2, 36 kDa (IGFBP2), mRNA [NM_000597]
A_23_P345733MT1K1.6855930.0002460.0013330.001333UpHomo sapiens metallothionein 1 K (MT1 K), mRNA [NM_176870]
A_23_P206760HP2.1006760.0002760.0014670.001467UpHomo sapiens haptoglobin (HP), mRNA [NM_005143]
A_23_P164057MFAP41.4731010.0006290.0029570.002957UpHomo sapiens microfibrillar-associated protein 4 (MFAP4), mRNA [NM_002404]
A_23_P99063LUM1.9641270.0007680.0034940.003494UpHomo sapiens lumican (LUM), mRNA [NM_002345]
A_23_P315364CXCL21.6285510.0008890.0039460.003946UpHomo sapiens chemokine (C-X-C motif) ligand 2 (CXCL2), mRNA [NM_002089]
A_23_P2492C1S1.4507370.001430.0058820.005882UpHomo sapiens complement component 1, s subcomponent (C1S), transcript variant 1, mRNA [NM_001734]
A_23_P345128SAA11.7416850.0027570.0099890.009989UpHomo sapiens serum amyloid A1 (SAA1), transcript variant 1, mRNA [NM_000331]
A_23_P124905NPTX11.4613040.0180370.0451680.045168UpHomo sapiens neuronal pentraxin I (NPTX1), mRNA [NM_002522]
A_23_P120502C20orf46-2.447242E-175.51E-155.51E-15DownHomo sapiens chromosome 20 open reading frame 46 (C20orf46), mRNA [NM_018354]
A_23_P14062NUP107- 1.485453.46E-167.05E-147.05E-14DownHomo sapiens nucleoporin 107 kDa (NUP107), mRNA [NM_020401]
A_23_P92765CCDC112-1.314851.14E-151.98E-131.98E-13DownCoiled-coil domain containing 112
A_23_P43675ZNF618-1.608962.28E-153.46E-133.46E-13DownHomo sapiens mRNA for KIAA1952 protein. [AB075832]
A_23_P148519TMEM29- 1.559892.38E-142.8E-122.8E-12DownHomo sapiens transmembrane protein 29 (TMEM29), mRNA [NM_014138]
A_23_P50108KNTC2-2.894656.5E-146.63E-126.63E-12DownHomo sapiens kinetochore associated 2 (KNTC2), mRNA [NM_006101]
A_23_P39116LIG1-2.008471.49E-131.32E-111.32E-11DownHomo sapiens ligase I, DNA, ATP-dependent (LIG1), mRNA [NM_000234]
A_23_P76718NEK3-1.117891.76E-131.55E-111.55E-11DownHomo sapiens NIMA (never in mitosis gene a)-related kinase 3 (NEK3), transcript variant 1, mRNA [NM_002498]
A_23_P122007C5ORF30-1.555851.95E-131.69E-111.69E-11DownChromosome 5 open reading frame 30
A_23_P90088ZNF443- 1.042413.87E-133.1E-113.1E-11DownHomo sapiens zinc finger protein 443 (ZNF443), mRNA [NM_005815]
A_23_P102571SLC2A4RG-2.243044.87E-133.79E-113.79E-11DownHomo sapiens SLC2A4 regulator (SLC2A4RG), mRNA [NM_020062]
A_23_P54617KIF22- 1.284217.09E-135.34E-115.34E-11DownHomo sapiens kinesin family member 22 (KIF22), mRNA [NM_007317]
A_23_P155815HCAP-G-2.737649.68E-137.05E-117.05E-11DownHomo sapiens chromosome condensation protein G (HCAP- G), mRNA [NM_022346]
Table 1 (continued)
Agiliant IdGene symbolLogFCP valueFDRT valueRegulationGene name
A_23_P71644FANCG-1.057851.39E-129.7E-119.7E-11DownHomo sapiens Fanconianemia, complementation group G (FANCG), mRNA [NM_004629]
A_23_P354297CHTF18- 1.649531.78E-121.19E-101.19E-10DownHomo sapiens CTF18, chromosome transmission fidelity factor 18 homolog (S. cerevisiae) (CHTF18), mRNA [NM_022092]
A_23_P155765HMGB2-1.39122.01E-121.33E-101.33E-10DownHomo sapiens high-mobility group box 2 (HMGB2), mRNA [NM_002129]
A_23_P259641EZH2-1.76153.1E-121.94E-101.94E-10DownHomo sapiens enhancer of zeste homolog 2 (Drosophila) (EZH2), transcript variant 1, mRNA [NM_004456]
A_23_P53276TIMELESS- 1.603473.32E-122.07E-102.07E-10DownHomo sapiens timeless homolog (Drosophila) (TIMELESS), mRNA [NM_003920]
A_23_P203891NCOR2-1.130674.17E-122.52E-102.52E-10DownHomo sapiens nuclear receptor co-repressor 2 (NCOR2), mRNA [NM_006312]
A_23_P28953DNMT3B-1.158124.48E-122.71E-102.71E-10DownHomo sapiens DNA (cytosine-5-)-methyltransferase 3 beta (DNMT3B), transcript variant 6, mRNA [NM_175850]
A_23_P397334PAQR4-1.501445.16E-123.07E-103.07E-10DownHomo sapiens progestin and adipoQ receptor family member IV (PAQR4), mRNA [NM_152341]
A_23_P153687XRCC1-1.221596.35E-123.68E-103.68E-10DownHomo sapiens X-ray repair complementing defective repair in Chinese hamster cells 1 (XRCC1), mRNA [NM_006297]
A_23_P55107ULK2-0.903079.25E-125.12E-105.12E-10DownHomo sapiens unc-51-like kinase 2 (C. elegans) (ULK2), mRNA [NM_014683]
A_23_P133123GAJ-2.230621.22E-116.53E-106.53E-10DownHomo sapiens GAJ protein (GAJ), mRNA [NM_032117]
A_23_P30243LRAP-2.026571.27E-116.72E-106.72E-10DownHomo sapiens leukocyte-derived arginine aminopeptidase (LRAP), mRNA [NM_022350]
A_23_P305121ANKRD23-0.900491.31E-116.88E-106.88E-10DownHomo sapiens ankyrin repeat domain 23 (ANKRD23), mRNA [NM_144994]
A_23_P385861CDCA2- 1.92542.4E-111.19E-091.19E-09DownHomo sapiens cell division cycle associated 2 (CDCA2), mRNA [NM_152562]
A_23_P103159C22orf18- 1.572322.58E-111.27E-091.27E-09DownHomo sapiens chromosome 22 open reading frame 18 (C22orf18), transcript variant 1, mRNA [NM_024053]
A_23_P7636PTTG1-1.66193.27E-111.54E-091.54E-09DownHomo sapiens pituitary tumor-transforming 1 (PTTG1), mRNA [NM_004219]
A_23_P208896CHAF1A-1.305013.48E-111.63E-091.63E-09DownHomo sapiens chromatin assembly factor 1, subunit A (p150) (CHAF1A), mRNA [NM_005483]
A_23_P200829SRGAP2- 1.429563.56E-111.66E-091.66E-09DownHomo sapiens mRNA for KIAA0456 protein, partial cds. [AB007925]
A_23_ P4922ZSWIM9ZSWIM9-0.982424.31E-111.97E-091.97E-09DownZinc finger SWIM-type containing 9
A_23_P250801MCM2-1.185184.49E-112.05E-092.05E-09DownHomo sapiens MCM2 minichromosome maintenance deficient 2, mitotin (S. cerevisiae) (MCM2), mRNA [NM_004526]
A_23_P170491TRIP-1.321024.85E-112.2E-092.2E-09DownHomo sapiens TRAF interacting protein (TRIP), mRNA [NM_005879]
A_23_P95302RFC5-1.271945.32E-112.38E-092.38E-09DownHomo sapiens replication factor C (activator 1) 5, 36.5 kDa (RFC5), transcript variant 2, mRNA [NM_181578]
A_23_P122197CCNB1- 1.847585.34E-112.39E-092.39E-09DownHomo sapiens cyclin B1 (CCNB1), mRNA [NM_031966]
A_23_P118246Pfs2- 1.395765.56E-112.48E-092.48E-09DownHomo sapiens DNA replication complex GINS protein PSF2 (Pfs2), mRNA [NM_016095]
A_23_P107764ZNF266-0.943935.61E-112.49E-092.49E-09DownHomo sapiens zinc finger protein 266 (ZNF266), mRNA [NM_006631]
A_23_P401CENPF-2.119325.85E-112.59E-092.59E-09DownHomo sapiens centromere protein F, 350/400 ka (mitosin) (CENPF), mRNA [NM_016343]
A_23_P90612MCM6-1.368686.96E-112.99E-092.99E-09DownHomo sapiens MCM6 minichromosome maintenance deficient 6 (MIS5 homolog, S. pombe) (S. cerevisiae) (MCM6), mRNA [NM_005915]
A_23_P145984TM4SF12-3.760517.04E-113.01E-093.01E-09DownHomo sapiens transmembrane 4 superfamily member 12 (TM4SF12), mRNA [NM_012338]
A_23_P157099ANLN-2.270027.33E-113.11E-093.11E-09DownHomo sapiens anillin, actin binding protein (scraps homolog, Drosophila) (ANLN), mRNA [NM_018685]
A_23_P159986MIR503HG-2.508868.32E-113.45E-093.45E-09DownMIR503 host gene
A_23_P254733MLF1IP-2.009238.56E-113.52E-093.52E-09DownHomo sapiens MLF1 interacting protein (MLF1IP), mRNA [NM_024629]
Table 1 (continued)
Agiliant IdGene symbolLogFCP valueFDRT valueRegulationGene name
A_23_P87810MAPKAPK5-1.195729.33E-113.81E-093.81E-09DownMitogen-activated protein kinase-activated protein kinase 5
A_23_P67771BARD1-1.117971.09E-104.39E-094.39E-09DownHomo sapiens BRCA1 associated RING domain 1 (BARD1), mRNA [NM_000465]
A_23_P136817KNTC1- 1.246211.43E-105.56E-095.56E-09DownHomo sapiens kinetochore associated 1 (KNTC1), mRNA [NM_014708]
A_23_P118815BIRC5-2.457761.51E-105.85E-095.85E-09DownHomo sapiens baculoviral IAP repeat-containing 5 (survivin) (BIRC5), mRNA [NM_001168]
A_23_P48029CLECSF6-1.297851.51E-105.86E-095.86E-09DownHomo sapiens C-type (calcium-dependent, carbohydrate- recognition domain) lectin, superfamily member 6 (CLECSF6), transcript variant 1, mRNA [NM_016184]
A_23_P253012GRAMD1C-2.288541.55E-105.96E-095.96E-09DownGRAM domain containing 1C
A_23_P429461FUK-1.077322.1E-107.9E-097.9E-09DownHomo sapiens fucokinase (FUK), mRNA [NM_145059]
A_23_P39574CCDC150-0.941552.37E-108.77E-098.77E-09DownCoiled-coil domain containing 150
A_23_P80902KNSL7-0.94832.65E-109.69E-099.69E-09DownHomo sapiens kinesin-like 7 (KNSL7), mRNA [NM_020242]
A_23_P61886TM4SF9- 1.473992.86E-101.04E-081.04E-08DownHomo sapiens cDNA FLJ31097 fis, clone IMR321000210. [AK055659]
A_23_P154730ZNF133-1.114422.96E-101.08E-081.08E-08DownHomo sapiens zinc finger protein 133 (clone pHZ-13) (ZNF133), mRNA [NM_003434]
A_23_P122052GPX8-1.962253.03E-101.09E-081.09E-08DownGlutathione peroxidase 8 (putative)
A_23_P50096TYMS-2.88823.04E-101.09E-081.09E-08DownHomo sapiens thymidylatesynthetase (TYMS), mRNA [NM_001071]
A_23_P431378C14orf80-0.914533.15E-101.13E-081.13E-08DownHomo sapiens chromosome 14 open reading frame 80 (C14orf80), mRNA [NM_173608]
A_23_P419213KIAA1407-0.909463.61E-101.27E-081.27E-08DownHomo sapiens KIAA1407 (KIAA1407), mRNA [NM_020817]
A_23_P204048DYRK2-1.004763.94E-101.38E-081.38E-08DownHomo sapiens dual specificity tyrosine-(Y)-phosphorylation regulated kinase 2 (DYRK2), transcript variant 2, mRNA [NM_006482]
A_23_P14184THSD1- 1.285324.1E-101.43E-081.43E-08DownHomo sapiens thrombospondin, type I, domain containing 1 (THSD1), transcript variant 1, mRNA [NM_018676]
A_23_P500390DONSON- 1.409034.41E-101.52E-081.52E-08DownHomo sapiens downstream neighbor of SON (DONSON), transcript variant 1, mRNA [NM_017613]
A_23_P379645BMF-1.187854.69E-101.61E-081.61E-08DownHomo sapiens Bcl2 modifying factor (BMF), transcript vari- ant 2, mRNA [NM_033503]
A_23_P356684ANLN-1.980764.76E-101.64E-081.64E-08DownHomo sapiens anillin, actin binding protein (scraps homolog, Drosophila) (ANLN), mRNA [NM_018685]
A_23_P27638ZNF700-0.899495.69E-101.92E-081.92E-08DownZinc finger protein 700
A_23_P329271MC1R-1.410835.74E-101.93E-081.93E-08DownHomo sapiens melanocortin 1 receptor (alpha melano- cyte stimulating hormone receptor) (MC1R), mRNA [NM_002386]
A_23_P74115RAD54L- 1.398246.12E-102.04E-082.04E-08DownHomo sapiens RAD54-like (S. cerevisiae) (RAD54L), mRNA [NM_003579]
A_23_P110742THOC3- 1.525076.74E-102.22E-082.22E-08DownHomo sapiens THO complex 3 (THOC3), mRNA [NM_032361]
A_23_P213592RNF44-1.203657.67E-102.48E-082.48E-08DownHomo sapiens ring finger protein 44 (RNF44), mRNA [NM_014901]
A_23_P134295NUDT1-1.15759.63E-102.98E-082.98E-08DownHomo sapiens nudix (nucleoside diphosphate linked moiety X)-type motif 1 (NUDT1), transcript variant 1, mRNA [NM_002452]
A_23_P386241C20orf55-0.899579.66E-102.98E-082.98E-08DownHomo sapiens chromosome 20 open reading frame 55 (C20orf55), transcript variant 1, mRNA [NM_031424]
A_23_P301981FLJ25402-0.937311.05E-093.19E-083.19E-08DownHomo sapiens hypothetical protein FLJ25402 (FLJ25402), mRNA [NM_001007090]
A_23_P65110RACGAP1- 1.882211.19E-093.54E-083.54E-08DownHomo sapiens RacGTPase activating protein 1 (RACGAP1), mRNA [NM_013277]
A_23_P74349CDCA1-2.096281.19E-093.54E-083.54E-08DownHomo sapiens cell division cycle associated 1 (CDCA1), transcript variant 1, mRNA [NM_145697]
A_23_P8663DMTF1-0.898631.36E-093.98E-083.98E-08DownHomo sapiens cyclin D binding myb-like transcription factor 1 (DMTF1), mRNA [NM_021145]
A_23_P154962KIAA1666-1.145061.48E-094.27E-084.27E-08DownHomo sapiens mRNA; cDNA DKFZp434H0735 (from clone DKFZp434H0735). [AL117509]
Table 1 (continued)
Agiliant IdGene symbolLogFCP valueFDRT valueRegulationGene name
A_23_P353717MGC24665- 1.429451.62E-094.63E-084.63E-08DownHomo sapiens hypothetical protein MGC24665 (MGC24665), mRNA [NM_152308]
A_23_P143147TCFL5-1.230551.66E-094.71E-084.71E-08DownHomo sapiens transcription factor-like 5 (basic helix-loop- helix) (TCFL5), mRNA [NM_006602]
A_23_P93032ZBED3-0.900631.66E-094.72E-084.72E-08DownHomo sapiens zinc finger, BED domain containing 3 (ZBED3), mRNA [NM_032367]
A_23_P99204MAPKAPK5- AS1-1.00821.81E-095.1E-085.1E-08DownMAPKAPK5 antisense RNA 1
A_23_P206059PRC1-1.238851.94E-095.42E-085.42E-08DownHomo sapiens protein regulator of cytokinesis 1 (PRC1), transcript variant 1, mRNA [NM_003981]
A_23_P89709Cep192- 1.234971.99E-095.56E-085.56E-08DownHomo sapiens centrosomal protein 192 kDa (Cep192), transcript variant 2, mRNA [NM_018069]
A_23_P104651CDCA5-1.807642.1E-095.83E-085.83E-08DownHomo sapiens cell division cycle associated 5 (CDCA5), mRNA [NM_080668]
A_23_P52017ASPM- 1.947562.3E-096.3E-086.3E-08DownHomo sapiens asp (abnormal spindle)-like, microcephaly associated (Drosophila) (ASPM), mRNA [NM_018136]
A_23_P259135NCOA6-1.085572.34E-096.39E-086.39E-08DownHomo sapiens nuclear receptor coactivator 6 (NCOA6), mRNA [NM_014071]
A_23_P257242KIAA0922-1.322242.51E-096.77E-086.77E-08DownHomo sapiens KIAA0922 protein (KIAA0922), mRNA [NM_015196]
A_23_P60024PTTG1-1.387182.65E-097.08E-087.08E-08DownHomo sapiens pituitary tumor-transforming 1 (PTTG1), mRNA [NM_004219]
A_23_P6582BX537558-1.015233.03E-097.97E-087.97E-08DownHomo sapiens mRNA; cDNA DKFZp686J1569 (from clone DKFZp686J1569). [BX537558]
A_23_P136222RRM2-1.431723.06E-098.03E-088.03E-08DownHomo sapiens ribonucleotidereductase M2 polypeptide (RRM2), mRNA [NM_001034]
A_23_P63789ZWINT-1.618153.22E-098.39E-088.39E-08DownHomo sapiens ZW10 interactor (ZWINT), transcript variant 2, mRNA [NM_032997]
A_23_P204689OCIL-0.934133.58E-099.25E-089.25E-08DownHomo sapiens lectin-like NK cell receptor (OCIL), transcript variant 1, mRNA [NM_013269]
A_23_P253281TBC1D8- 1.548193.92E-091E-071E-07DownHomo sapiens TBC1 domain family, member 8 (with GRAM domain) (TBC1D8), mRNA [NM_007063]
A_23_P18196RFC4-1.396514.03E-091.03E-071.03E-07DownHomo sapiens replication factor C (activator 1) 4, 37 kDa (RFC4), transcript variant 1, mRNA [NM_002916]
A_23_P254441LOC155060-1.166064.16E-091.06E-071.06E-07DownHomo sapiens hypothetical protein LOC155060 (LOC155060), mRNA [NM_001004302]
A_23_P45365COL4A5- 1.777244.43E-091.12E-071.12E-07DownHomo sapiens collagen, type IV, alpha 5 (Alport syndrome) (COL4A5), transcript variant 2, mRNA [NM_033380]
A_23_P124417BUB1- 1.48234.76E-091.19E-071.19E-07DownHomo sapiens BUB1 budding uninhibited by benzimidazoles 1 homolog (yeast) (BUB1), mRNA [NM_004336]
A_23_P372984MGC24975-1.210315.97E-091.45E-071.45E-07DownHomo sapiens hypothetical protein MGC24975 (MGC24975), mRNA [NM_153359]
A_23_P163546TAF1C-0.993945.98E-091.45E-071.45E-07DownHomo sapiens TATA box binding protein (TBP)-associated factor, RNA polymerase I, C, 110 kDa (TAF1C), transcript variant 1, mRNA [NM_005679]
A_23_P19102GALNT10-0.99156.18E-091.49E-071.49E-07DownHomo sapiens cDNA FLJ11715 fis, clone HEMBA1005223. [AK021777]
A_23_P155989FKSG14-1.382246.21E-091.5E-071.5E-07DownHomo sapiens leucine zipper protein FKSG14 (FKSG14), mRNA [NM_022145]
A_23_P253752FAM54A-1.336666.97E-091.65E-071.65E-07DownHomo sapiens family with sequence similarity 54, member A (FAM54A), mRNA [NM_138419]
A_23_P210482ADA-0.998328.29E-091.92E-071.92E-07DownHomo sapiens adenosine deaminase (ADA), mRNA [NM_000022]
A_23_P304420TIGD2-0.924118.59E-091.98E-071.98E-07DownHomo sapiens tigger transposable element derived 2 (TIGD2), mRNA [NM_145715]
A_23_P102471MSH2- 1.012418.78E-092.01E-072.01E-07DownHomo sapiens mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli) (MSH2), mRNA [NM_000251]
A_23_P415443BRRN1- 1.076479.48E-092.13E-072.13E-07DownHomo sapiens barren homolog (Drosophila) (BRRN1), mRNA [NM_015341]
A_23_P117852KIAA0101-2.044119.48E-092.13E-072.13E-07DownHomo sapiens KIAA0101 (KIAA0101), mRNA [NM_014736]
Table 1 (continued)
Agiliant IdGene symbolLogFCP valueFDRT valueRegulationGene name
A_23_P118582TBPIP-1.170559.83E-092.2E-072.2E-07DownHomo sapiens TBP-1 interacting protein (TBPIP), mRNA [NM_013290]
A_23_P49878PIMREG- 1.422831.06E-082.33E-072.33E-07DownPICALM interacting mitotic regulator
A_23_P49546GRIN2C-2.647081.15E-082.52E-072.52E-07DownHomo sapiens glutamate receptor, ionotropic, N-methyl D-aspartate 2C (GRIN2C), mRNA [NM_000835]
A_23_P169518RABEP2-1.313261.25E-082.71E-072.71E-07DownHomo sapiens rabaptin, RAB GTPase binding effector protein 2 (RABEP2), mRNA [NM_024816]
A_23_P166336TMEM191A-1.584751.25E-082.71E-072.71E-07Downtransmembrane protein 191A (pseudogene)
A_23_P107421TK1- 1.874771.27E-082.75E-072.75E-07DownHomo sapiens thymidine kinase 1, soluble (TK1), mRNA [NM_003258]
A_23_P209032ZNF302-0.995791.39E-082.98E-072.98E-07DownHomo sapiens zinc finger protein 302 (ZNF302), mRNA [NM_018675]
A_23_P129577TIGD7- 1.034431.4E-082.98E-072.98E-07DownHomo sapiens tigger transposable element derived 7 (TIGD7), mRNA [NM_033208]
A_23_P384056CCDC14-0.968081.44E-083.06E-073.06E-07DownHomo sapiens hypothetical protein FLJ12892 (FLJ12892), mRNA [NM_022757]
A_23_P129014C14orf143- 1.047371.57E-083.3E-073.3E-07DownHomo sapiens chromosome 14 open reading frame 143 (C14orf143), mRNA [NM_145231]
A_23_P145016BRD8-1.130161.61E-083.37E-073.37E-07DownHomo sapiens bromodomain containing 8 (BRD8), transcript variant 1, mRNA [NM_006696]
A_23_P15582XYLT2-1.00131.67E-083.48E-073.48E-07DownHomo sapiens xylosyltransferase II (XYLT2), mRNA [NM_022167]
A_23_P259586TTK- 1.452441.71E-083.57E-073.57E-07DownHomo sapiens TTK protein kinase (TTK), mRNA [NM_003318]
A_23_P57306CHAF1B-1.294561.98E-084.06E-074.06E-07DownHomo sapiens chromatin assembly factor 1, subunit B (p60) (CHAF1B), mRNA [NM_005441]
A_23_P37776FHOD1-0.89962.06E-084.2E-074.2E-07DownHomo sapiens formin homology 2 domain containing 1 (FHOD1), mRNA [NM_013241]
A_23_P134650PTCD1-0.907042.07E-084.21E-074.21E-07DownHomo sapiens pentatricopeptide repeat domain 1 (PTCD1), mRNA [NM_015545]
A_23_P88731RAD51-1.184032.11E-084.29E-074.29E-07DownHomo sapiens RAD51 homolog (RecA homolog, E. coli) (S. cerevisiae) (RAD51), transcript variant 1, mRNA [NM_002875]
A_23_P168882TP53INP1-0.968532.12E-084.3E-074.3E-07DownHomo sapiens tumor protein p53 inducible nuclear protein 1 (TP53INP1), mRNA [NM_033285]
A_23_P10385RAMP-1.000772.26E-084.52E-074.52E-07DownHomo sapiens RA-regulated nuclear matrix-associated protein (RAMP), mRNA [NM_016448]
A_23_P52589C11orf13-1.25862.34E-084.65E-074.65E-07DownHomo sapiens chromosome 11 open reading frame 13 (C11orf13), mRNA [NM_003475]
A_23_P87769FLJ20641-1.143192.44E-084.83E-074.83E-07DownHomo sapiens hypothetical protein FLJ20641 (FLJ20641), mRNA [NM_017915]
A_23_P4626ZNF606-0.929072.61E-085.12E-075.12E-07DownHomo sapiens zinc finger protein 606 (ZNF606), mRNA [NM_025027]
A_23_P215525OSBPL3- 1.279722.83E-085.51E-075.51E-07DownHomo sapiens oxysterol binding protein-like 3 (OSBPL3), transcript variant 5, mRNA [NM_145323]
A_23_P146456CTSL2-1.861763E-085.79E-075.79E-07DownHomo sapiens cathepsin L2 (CTSL2), mRNA [NM_001333]
A_23_P82699PBK- 1.829063.3E-086.3E-076.3E-07DownHomo sapiens PDZ binding kinase (PBK), mRNA [NM_018492]
A_23_P408108MTERF-0.91423.82E-087.15E-077.15E-07DownHomo sapiens transcription termination factor, mitochondrial (MTERF), nuclear gene encoding mitochondrial protein, mRNA [NM_006980]
A_23_P214059NR3C1- 1.026084.27E-087.89E-077.89E-07DownHomo sapiens nuclear receptor subfamily 3, group C, member 1 (glucocorticoid receptor) (NR3C1), mRNA [NM_000176]
A_23_P303876APOBEC3A- 1.072295.18E-089.38E-079.38E-07DownHomo sapiens apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A (APOBEC3A), mRNA [NM_145699]
A_23_P138507CDC2-1.751365.21E-089.41E-079.41E-07DownHomo sapiens cell division cycle 2, G1 to S and G2 to M (CDC2), transcript variant 1, mRNA [NM_001786]
A_23_P168771KIAA1505- 1.026575.28E-089.52E-079.52E-07DownHomo sapiens KIAA1505 protein (KIAA1505), mRNA [NM_020879]
Table 1 (continued)
Agiliant IdGene symbolLogFCP valueFDRT valueRegulationGene name
A_23_P43595KIF24-1.049845.65E-081.01E-061.01E-06DownHomo sapiens cDNA FLJ10933 fis, clone OVARC1000605. [AK001795]
A_23_P151405CKAP2- 1.415575.78E-081.03E-061.03E-06DownHomo sapiens cytoskeleton associated protein 2 (CKAP2), mRNA [NM_018204]
A_23_P88331DLG7- 1.582795.8E-081.04E-061.04E-06DownHomo sapiens discs, large homolog 7 (Drosophila) (DLG7), mRNA [NM_014750]
A_23_P323930TM4SF9-1.102126.09E-081.08E-061.08E-06DownHomo sapiens transmembrane 4 superfamily member 9 (TM4SF9), mRNA [NM_005723]
A_23_P160427FLJ14146- 1.473357.1E-081.23E-061.23E-06DownHomo sapiens hypothetical protein FLJ14146 (FLJ14146), mRNA [NM_024709]
A_23_P382775BBC3- 1.809487.15E-081.24E-061.24E-06DownHomo sapiens BCL2 binding component 3 (BBC3), mRNA [NM_014417]
A_23_P103765FCER1A-1.926347.33E-081.26E-061.26E-06DownHomo sapiens Fc fragment of IgE, high affinity I, receptor for; alpha polypeptide (FCER1A), mRNA [NM_002001]
A_23_P217755APXL-0.891877.46E-081.28E-061.28E-06DownHomo sapiens apical protein-like (Xenopuslaevis) (APXL), mRNA [NM_001649]
A_23_P334192FLJ90709-0.902367.58E-081.3E-061.3E-06DownHomo sapiens hypothetical protein FLJ90709 (FLJ90709), mRNA [NM_173514]
A_23_P145657STAG3-1.575658.01E-081.36E-061.36E-06DownHomo sapiens stromal antigen 3 (STAG3), mRNA [NM_012447]
A_23_P92441MAD2L1- 1.837038.8E-081.48E-061.48E-06DownHomo sapiens MAD2 mitotic arrest deficient-like 1 (yeast) (MAD2L1), mRNA [NM_002358]
A_23_P335898STK36-1.005249.22E-081.53E-061.53E-06DownHomo sapiens serine/threonine kinase 36 (fused homolog, Drosophila) (STK36), mRNA [NM_015690]
A_23_P134684HMBOX1-1.676139.84E-081.62E-061.62E-06DownHomeobox containing 1
A_23_P419712BTBD11- 1.602421.08E-071.76E-061.76E-06DownHomo sapiens BTB (POZ) domain containing 11 (BTBD11), mRNA [NM_152322]
A_23_P57379CDC45L-0.993321.1E-071.79E-061.79E-06DownHomo sapiens CDC45 cell division cycle 45-like (S. cerevi- siae) (CDC45L), mRNA [NM_003504]
A_23_P7873MCM3- 1.062241.18E-071.91E-061.91E-06DownHomo sapiens MCM3 minichromosome maintenance defi- cient 3 (S. cerevisiae) (MCM3), mRNA [NM_002388]
A_23_P30805HIST1H4J-1.093831.19E-071.93E-061.93E-06DownHomo sapiens histone 1, H4j (HIST1H4J), mRNA [NM_021968]
A_23_P118834TOP2A- 1.560041.19E-071.93E-061.93E-06DownHomo sapiens topoisomerase (DNA) II alpha 170 kDa (TOP2A), mRNA [NM_001067]
A_23_P76998KIAA1036-0.909191.24E-072E-062E-06DownHomo sapiens KIAA1036 (KIAA1036), mRNA [NM_014909]
A_23_P210827C20orf36-0.988871.26E-072.02E-062.02E-06DownHomo sapiens chromosome 20 open reading frame 36 (C20orf36), mRNA [NM_018257]
A_23_P65757CCNB2-1.900591.28E-072.06E-062.06E-06DownHomo sapiens cyclin B2 (CCNB2), mRNA [NM_004701]
A_23_P92860UNG2-1.252461.31E-072.1E-062.1E-06DownHomo sapiens uracil-DNA glycosylase 2 (UNG2), mRNA [NM_021147]
A_23_P72551ULK1-1.113031.39E-072.22E-062.22E-06DownHomo sapiens unc-51-like kinase 1 (C. elegans) (ULK1), mRNA [NM_003565]
A_23_P149535SLC27A3-0.940761.4E-072.23E-062.23E-06DownHomo sapiens solute carrier family 27 (fatty acid trans- porter), member 3 (SLC27A3), mRNA [NM_024330]
A_23_P215634IGFBP3-1.719131.43E-072.26E-062.26E-06DownHomo sapiens insulin-like growth factor binding protein 3 (IGFBP3), mRNA [NM_000598]
A_23_P381979OGT- 1.403041.51E-072.37E-062.37E-06DownHomo sapiens O-linked N-acetylglucosamine (GlcNAc) transferase (UDP-N-acetylglucosamine:polypeptide- N-acetylglucosaminyltransferase) (OGT), transcript variant 3, mRNA [NM_003605]
A_23_P435636DAND5-1.11081.51E-072.38E-062.38E-06DownHomo sapiens DAN domain family, member 5 (DAND5), mRNA [NM_152654]
A_23_P99292RAD51AP1- 1.077041.82E-072.78E-062.78E-06DownHomo sapiens RAD51 associated protein 1 (RAD51AP1), mRNA [NM_006479]
A_23_P98930FLJ10652-0.99091.92E-072.9E-062.9E-06DownHomo sapiens hypothetical protein FLJ10652 (FLJ10652), mRNA [NM_018169]
A_23_P111112VARS2L-0.943592.01E-073.01E-063.01E-06DownHomo sapiens valyl-tRNAsynthetase 2-like (VARS2L), mRNA [NM_020442]
A_23_P156417CAP2-1.226782.19E-073.25E-063.25E-06DownHomo sapiens CAP, adenylatecyclase-associated protein, 2 (yeast) (CAP2), mRNA [NM_006366]
Table 1 (continued)
Agiliant IdGene symbolLogFCP valueFDRT valueRegulationGene name
A_23_P94422MELK- 1.480722.29E-073.39E-063.39E-06DownHomo sapiens maternal embryonic leucine zipper kinase (MELK), mRNA [NM_014791]
A_23_P54055JUB-1.331772.31E-073.41E-063.41E-06DownHomo sapiens jub, ajuba homolog (Xenopuslaevis) (JUB), transcript variant 1, mRNA [NM_032876]
A_23_P209200CCNE1-1.673892.32E-073.42E-063.42E-06DownHomo sapiens cyclin E1 (CCNE1), transcript variant 1, mRNA [NM_001238]
A_23_P89509SPAG5- 1.343972.38E-073.5E-063.5E-06DownHomo sapiens sperm associated antigen 5 (SPAG5), mRNA [NM_006461]
A_23_P27023RAB11FIP4-1.941552.43E-073.56E-063.56E-06DownHomo sapiens RAB11 family interacting protein 4 (class II) (RAB11FIP4), mRNA [NM_032932]
A_23_P115482HSPC150-1.289622.49E-073.64E-063.64E-06DownHomo sapiens HSPC150 protein similar to ubiquitin-conju- gating enzyme (HSPC150), mRNA [NM_014176]
A_23_P7596MYO10- 1.597442.81E-074.05E-064.05E-06DownHomo sapiens myosin X (MYO10), mRNA [NM_012334]
A_23_P35219NEK2-1.074532.83E-074.07E-064.07E-06DownHomo sapiens NIMA (never in mitosis gene a)-related kinase 2 (NEK2), mRNA [NM_002497]
A_23_P68610TPX2-1.031482.98E-074.25E-064.25E-06DownHomo sapiens TPX2, microtubule-associated protein homolog (Xenopuslaevis) (TPX2), mRNA [NM_012112]
A_23_P64689USP52-0.920983E-074.27E-064.27E-06DownHomo sapiens ubiquitin specific protease 52 (USP52), mRNA [NM_014871]
A_23_P204158RNFT2-1.038543.19E-074.51E-064.51E-06DownRing finger protein, transmembrane 2
A_23_P403334SLAC2-B-1.281883.32E-074.67E-064.67E-06DownHomo sapiens SLAC2-B (SLAC2-B), mRNA [NM_015065]
A_23_P85780PHGDH-0.947423.33E-074.67E-064.67E-06DownHomo sapiens phosphoglycerate dehydrogenase (PHGDH), mRNA [NM_006623]
A_23_P428840TMEM44-0.992973.37E-074.72E-064.72E-06DownHomo sapiens transmembrane protein 44 (TMEM44), tran- script variant 1, mRNA [NM_138399]
A_23_P23611AMY1A-1.325043.58E-074.97E-064.97E-06DownHomo sapiens amylase, alpha 1A; salivary (AMY1A), tran- script variant 1, mRNA [NM_004038]
A_23_P323751C20orf129- 1.435233.59E-074.99E-064.99E-06DownHomo sapiens chromosome 20 open reading frame 129 (C20orf129), mRNA [NM_030919]
A_23_P110473BIRC1-1.075673.63E-075.04E-065.04E-06DownHomo sapiens baculoviral IAP repeat-containing 1 (BIRC1), mRNA [NM_004536]
A_23_P211926WNT5A-1.075533.96E-075.44E-065.44E-06DownHomo sapiens wingless-type MMTV integration site family, member 5A (WNT5A), mRNA [NM_003392]
A_23_P93311DDR1-0.900594E-075.48E-065.48E-06DownHomo sapiens discoidin domain receptor family, member 1 (DDR1), transcript variant 3, mRNA [NM_013994]
A_23_P253052CD99L2-0.936624.01E-075.49E-065.49E-06DownHomo sapiens CD99 antigen-like 2 (CD99L2), mRNA [NM_031462]
A_23_P60079ANGPT2- 1.488464.04E-075.52E-065.52E-06DownHomo sapiens angiopoietin 2 (ANGPT2), mRNA [NM_001147]
A_23_P51085Spc25-1.222264.38E-075.91E-065.91E-06DownHomo sapiens kinetochore protein Spc25 (Spc25), mRNA [NM_020675]
A_23_P52278KIF11-0.925314.41E-075.93E-065.93E-06DownHomo sapiens kinesin family member 11 (KIF11), mRNA [NM_004523]
A_23_P50456POLD1-0.916214.41E-075.93E-065.93E-06DownHomo sapiens polymerase (DNA directed), delta 1, catalytic subunit 125 kDa (POLD1), mRNA [NM_002691]
A_23_P375CDCA8-0.9094.51E-076.04E-066.04E-06DownHomo sapiens cell division cycle associated 8 (CDCA8), mRNA [NM_018101]
A_23_P161507MTL5-1.223814.86E-076.44E-066.44E-06DownHomo sapiens metallothionein-like 5, testis-specific (tesmin) (MTL5), mRNA [NM_004923]
A_23_P19712GMNN-1.178614.96E-076.56E-066.56E-06DownHomo sapiens geminin, DNA replication inhibitor (GMNN), mRNA [NM_015895]
A_23_P92794C5orf13-1.46055.51E-077.18E-067.18E-06DownHomo sapiens chromosome 5 open reading frame 13 (C5orf13), mRNA [NM_004772]
A_23_P111125HCP5- 1.027015.54E-077.2E-067.2E-06DownHomo sapiens HLA complex P5 (HCP5), mRNA [NM_006674]
A_23_P501372SMCR7-0.93395.82E-077.51E-067.51E-06DownHomo sapiens Smith-Magenis syndrome chromosome region, candidate 7 (SMCR7), transcript variant 1, mRNA [NM_139162]
A_23_P86330IER5-0.9316.3E-078.07E-068.07E-06DownHomo sapiens immediate early response 5 (IER5), mRNA [NM_016545]
A_23_P143184MYBL2-0.940486.36E-078.13E-068.13E-06DownHomo sapiens v-mybmyeloblastosis viral oncogene homolog (avian)-like 2 (MYBL2), mRNA [NM_002466]
Table 1 (continued)
Agiliant IdGene symbolLogFCP valueFDRT valueRegulationGene name
A_23_P379614OIP5-1.307256.49E-078.29E-068.29E-06DownHomo sapiens Opa interacting protein 5 (OIP5), mRNA [NM_007280]
A_23_P350689ZDHHC23-0.922496.62E-078.43E-068.43E-06DownHomo sapiens zinc finger, DHHC domain containing 23 (ZDHHC23), mRNA [NM_173570]
A_23_P109539APOBEC3B- 1.944656.67E-078.47E-068.47E-06DownHomo sapiens apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3B (APOBEC3B), mRNA [NM_004900]
A_23_P89780LAMA3-0.898936.86E-078.69E-068.69E-06DownHomo sapiens laminin, alpha 3 (LAMA3), transcript variant 2, mRNA [NM_000227]
A_23_P23303EXO1- 1.029687.3E-079.16E-069.16E-06DownHomo sapiens exonuclease 1 (EXO1), transcript variant 3, mRNA [NM_003686]
A_23_P27490DNMT1-0.934777.49E-079.39E-069.39E-06DownHomo sapiens DNA (cytosine-5-)-methyltransferase 1 (DNMT1), mRNA [NM_001379]
A_23_P348298SHD1-0.900227.57E-079.48E-069.48E-06DownHomo sapiens Sac3 homology domain 1 (S. cerevisiae) (SHD1), mRNA [NM_013299]
A_23_P115872C10orf3- 1.594078.01E-079.97E-069.97E-06DownHomo sapiens chromosome 10 open reading frame 3 (C10orf3), mRNA [NM_018131]
A_23_P33898MAGED2- 1.404658.82E-071.08E-051.08E-05DownHomo sapiens melanoma antigen family D, 2 (MAGED2), transcript variant 3, mRNA [NM_201222]
A_23_P94030LAMB1-1.545669.28E-071.13E-051.13E-05DownHomo sapiens laminin, beta 1 (LAMB1), mRNA [NM_002291]
A_23_P323761T3JAM-1.230911.01E-061.21E-051.21E-05DownHomo sapiens TRAF3-interacting Jun N-terminal kinase (JNK)-activating modulator (T3JAM), mRNA [NM_025228]
A_23_P70007HMMR-1.086971.02E-061.23E-051.23E-05DownHomo sapiens hyaluronan-mediated motility recep- tor (RHAMM) (HMMR), transcript variant 1, mRNA [NM_012484]
A_23_P130376FAM38B- 1.469941.07E-061.28E-051.28E-05DownHomo sapiens family with sequence similarity 38, member B (FAM38B), mRNA [NM_022068]
A_23_P92719RAI14-0.94751.08E-061.28E-051.28E-05DownHomo sapiens retinoic acid induced 14 (RAI14), mRNA [NM_015577]
A_23_P118203ZG16B-1.981431.08E-061.28E-051.28E-05DownZymogen granule protein 16B
A_23_P65918ITPKA- 1.224091.09E-061.29E-051.29E-05DownHomo sapiens inositol 1,4,5-trisphosphate 3-kinase A (ITPKA), mRNA [NM_002220]
A_23_P58819RANBP17-1.018771.1E-061.31E-051.31E-05DownHomo sapiens RAN-binding protein 17 (RANBP17), mRNA [NM_022897]
A_23_P150667KIF18A-1.061511.16E-061.37E-051.37E-05DownHomo sapiens kinesin family member 18A (KIF18A), mRNA [NM_031217]
A_23_P214281C6orf33-1.007571.18E-061.39E-051.39E-05DownHomo sapiens chromosome 6 open reading frame 33 (C6orf33), mRNA [NM_133367]
A_23_P8013HIST1H2BL-1.19941.26E-061.46E-051.46E-05DownHomo sapiens histone 1, H2bl (HIST1H2BL), mRNA [NM_003519]
A_23_P501435CSRP2BP-0.923661.27E-061.47E-051.47E-05DownHomo sapiens CSRP2 binding protein (CSRP2BP), tran- script variant 1, mRNA [NM_020536]
A_23_P88678C15orf27-1.71151.28E-061.48E-051.48E-05DownHomo sapiens chromosome 15 open reading frame 27 (C15orf27), mRNA [NM_152335]
A_23_P402081HIST1H2BN-0.980811.3E-061.49E-051.49E-05DownHomo sapiens histone 1, H2bn (HIST1H2BN), mRNA [NM_003520]
A_23_P167017POPDC2- 1.094661.37E-061.56E-051.56E-05DownHomo sapiens popeye domain containing 2 (POPDC2), mRNA [NM_022135]
A_23_P90333ZNF404-2.163671.44E-061.63E-051.63E-05DownPREDICTED: Homo sapiens zinc finger protein 404 (ZNF404), mRNA [XM_292765]
A_23_P26883MMP28- 1.022641.44E-061.63E-051.63E-05DownHomo sapiens matrix metalloproteinase 28 (MMP28), tran- script variant 2, mRNA [NM_032950]
A_23_P348257ARK5-1.231851.45E-061.65E-051.65E-05DownHomo sapiens AMP-activated protein kinase family member 5 (ARK5), mRNA [NM_014840]
A_23_P3911PLXDC1- 1.241271.56E-061.76E-051.76E-05DownHomo sapiens plexin domain containing 1 (PLXDC1), mRNA [NM_020405]
A_23_P119095PPP1R13L-0.913271.6E-061.79E-051.79E-05DownHomo sapiens protein phosphatase 1, regulatory (inhibitor) subunit 13 like (PPP1R13L), mRNA [NM_006663]
A_23_P47885LRIG3-1.343851.63E-061.82E-051.82E-05DownHomo sapiens leucine-rich repeats and immunoglobulin-like domains 3 (LRIG3), mRNA [NM_153377]
Table 1 (continued)
Agiliant IdGene symbolLogFCP valueFDRT valueRegulationGene name
A_23_P213424ENC1- 1.439181.67E-061.85E-051.85E-05DownHomo sapiens ectodermal-neural cortex (with BTB-like domain) (ENC1), mRNA [NM_003633]
A_23_P217236HMGB3- 1.205251.87E-062.04E-052.04E-05DownHomo sapiens high-mobility group box 3 (HMGB3), mRNA [NM_005342]
A_23_P140434MYO5C- 1.065591.94E-062.11E-052.11E-05DownHomo sapiens myosin VC (MYO5C), mRNA [NM_018728]
A_23_P31677MGC40214-1.134031.95E-062.11E-052.11E-05DownHomo sapiens cDNA FLJ23887 fis, clone LNG14332. [AK074467]
A_23_P206441FANCA-0.960162.03E-062.18E-052.18E-05DownHomo sapiens Fanconianemia, complementation group A (FANCA), mRNA [NM_000135]
A_23_P253873RAM2-0.972462.06E-062.21E-052.21E-05DownHomo sapiens transcription factor RAM2 (RAM2), mRNA [NM_018719]
A_23_P68547MCM8-0.988922.13E-062.28E-052.28E-05DownHomo sapiens MCM8 minichromosome maintenance deficient 8 (S. cerevisiae) (MCM8), transcript variant 1, mRNA [NM_032485]
A_23_P24083PNLIPRP2-1.132622.14E-062.28E-052.28E-05DownHomo sapiens pancreatic lipase-related protein 2 (PNLIPRP2), mRNA [NM_005396]
A_23_P14986HSD11B2-0.989912.24E-062.38E-052.38E-05DownHomo sapiens hydroxysteroid (11-beta) dehydrogenase 2 (HSD11B2), mRNA [NM_000196]
A_23_P48669CDKN3-1.36192.34E-062.47E-052.47E-05DownHomo sapiens cyclin-dependent kinase inhibitor 3 (CDK2- associated dual specificity phosphatase) (CDKN3), mRNA [NM_005192]
A_23_P334608GUSB-0.893832.38E-062.5E-052.5E-05DownHomo sapiens glucuronidase, beta (GUSB), mRNA [NM_000181]
A_23_P79429DKFZp762E1312-1.080642.42E-062.54E-052.54E-05DownHomo sapiens hypothetical protein DKFZp762E1312 (DKFZp762E1312), mRNA [NM_018410]
A_23_P210191U96396-1.076482.42E-062.54E-052.54E-05DownHomo sapiens anti-streptococcal/anti-myosin immunoglobu- lin kappa light chain variable region mRNA, partial cds. [U96396]
A_23_P32661#N/A-0.903752.52E-062.64E-052.64E-05DownUnknown
A_23_P159011#N/A- 1.475442.56E-062.67E-052.67E-05DownUnknown
A_23_P204630NTN4-1.26792.77E-062.88E-052.88E-05DownHomo sapiens netrin 4 (NTN4), mRNA [NM_021229]
A_23_P6741IQSEC1-1.068332.78E-062.89E-052.89E-05DownHomo sapiens IQ motif and Sec7 domain 1 (IQSEC1), mRNA [NM_014869]
A_23_P213050HPGD-1.263012.85E-062.94E-052.94E-05DownHomo sapiens hydroxyprostaglandin dehydrogenase 15-(NAD) (HPGD), mRNA [NM_000860]
A_23_P123276FZD6-0.891843E-063.07E-053.07E-05DownHomo sapiens frizzled homolog 6 (Drosophila) (FZD6), mRNA [NM_003506]
A_23_P251421CDCA7-1.28783.03E-063.09E-053.09E-05DownHomo sapiens cell division cycle associated 7 (CDCA7), transcript variant 1, mRNA [NM_031942]
A_23_P144835ESM1-2.308453.08E-063.14E-053.14E-05DownHomo sapiens endothelial cell-specific molecule 1 (ESM1), mRNA [NM_007036]
A_23_P97283PAQR6-0.899623.32E-063.34E-053.34E-05DownHomo sapiens progestin and adipoQ receptor family member VI (PAQR6), transcript variant 1, mRNA [NM_024897]
A_23_P58604MRNIP-1.127953.32E-063.34E-053.34E-05DownMRN complex interacting protein
A_23_P257704HSPB1-1.105063.58E-063.57E-053.57E-05DownHomo sapiens heat shock 27 kDa protein 1 (HSPB1), mRNA [NM_001540]
A_23_P373119HMG4L-1.185873.88E-063.82E-053.82E-05DownHomo sapiens high-mobility group (nonhistone chromo- somal) protein 4-like (HMG4L) on chromosome 20 [NR_002165]
A_23_P359540HIST1H4F-0.983553.92E-063.85E-053.85E-05DownHomo sapiens histone 1, H4f (HIST1H4F), mRNA [NM_003540]
A_23_P366216HIST1H2BH-1.183473.94E-063.87E-053.87E-05DownHomo sapiens histone 1, H2bh (HIST1H2BH), mRNA [NM_003524]
A_23_P213527GPR150-1.104033.97E-063.89E-053.89E-05DownG protein-coupled receptor 150
A_23_P160518TRIM45-1.113783.98E-063.9E-053.9E-05DownHomo sapiens tripartite motif-containing 45 (TRIM45), mRNA [NM_025188]
A_23_P92222MUC20-0.914053.98E-063.9E-053.9E-05DownHomo sapiens mucin 20 (MUC20), mRNA [NM_152673]
A_23_P30813HIST1H4K-1.206624.04E-063.94E-053.94E-05DownHomo sapiens histone 1, H4k (HIST1H4K), mRNA [NM_003541]
A_23_P134835ChGn- 1.540344.48E-064.32E-054.32E-05DownHomo sapiens chondroitin beta1,4 N-acetylgalactosaminyl- transferase (ChGn), mRNA [NM_018371]
Table 1 (continued)
Agiliant IdGene symbolLogFCP valueFDRT valueRegulationGene name
A_23_P12363ROR1-1.13454.57E-064.4E-054.4E-05DownHomo sapiens receptor tyrosine kinase-like orphan receptor 1 (ROR1), mRNA [NM_005012]
A_23_P403898PTPN3-1.019534.98E-064.74E-054.74E-05DownHomo sapiens protein tyrosine phosphatase, non-receptor type 3 (PTPN3), mRNA [NM_002829]
A_23_P401718CCDC74A-1.808575.72E-065.36E-055.36E-05DownCoiled-coil domain containing 74A
A_23_P87742HOM-TES-103-1.07775.73E-065.36E-055.36E-05DownHomo sapiens HOM-TES-103 tumor antigen-like (HOM- TES-103), transcript variant 2, mRNA [NM_080730]
A_23_P16976ANXA4-1.28675.87E-065.48E-055.48E-05DownHomo sapiens annexin A4 (ANXA4), mRNA [NM_001153]
A_23_P421664CAP2-1.134846.53E-066.02E-056.02E-05DownHomo sapiens CAP, adenylatecyclase-associated protein, 2 (yeast) (CAP2), mRNA [NM_006366]
A_23_P323685HIST1H4H-0.966377.13E-066.5E-056.5E-05DownHomo sapiens histone 1, H4 h (HIST1H4H), mRNA [NM_003543]
A_23_P58706SPINK5L3-2.02787.14E-066.51E-056.51E-05DownHomo sapiens cDNA FLJ10658 fis, clone NT2RP2006052. [AK001520]
A_23_P112341C9orf76- 1.047467.21E-066.56E-056.56E-05DownHomo sapiens chromosome 9 open reading frame 76 (C9orf76), mRNA [NM_024945]
A_23_P115785FANK1-0.96677.45E-066.71E-056.71E-05DownHomo sapiens fibronectin type 3 and ankyrin repeat domains 1 (FANK1), mRNA [NM_145235]
A_23_P24716HSPA5BP1- 1.433867.74E-066.94E-056.94E-05DownHomo sapiens heat shock 70 kDa protein 5 (glucose- regulated protein, 78 kDa) binding protein 1 (HSPA5BP1), transcript variant 1, mRNA [NM_017870]
A_23_P30275PCYOX1L-1.149798.11E-067.23E-057.23E-05DownPrenylcysteine oxidase 1 like
A_23_P59069HIST1H2BO-1.13068.18E-067.28E-057.28E-05DownHomo sapiens histone 1, H2bo (HIST1H2BO), mRNA [NM_003527]
A_23_P12204AMY2A-1.050718.52E-067.53E-057.53E-05DownHomo sapiens amylase, alpha 2A; pancreatic (AMY2A), mRNA [NM_000699]
A_23_P200792NOTCH2-0.925328.58E-067.58E-057.58E-05DownHomo sapiens Notch homolog 2 (Drosophila) (NOTCH2), mRNA [NM_024408]
A_23_P387471MICB-0.998859.12E-067.97E-057.97E-05DownHomo sapiens MHC class I polypeptide-related sequence B (MICB), mRNA [NM_005931]
A_23_P42908FLJ90586-1.158859.32E-068.12E-058.12E-05DownHomo sapiens hypothetical protein FLJ90586 (FLJ90586), mRNA [NM_153345]
A_23_P41634ANKRA2-1.181579.54E-068.29E-058.29E-05DownHomo sapiens ankyrin repeat, family A (RFXANK-like), 2 (ANKRA2), mRNA [NM_023039]
A_23_P35871E2F8-1.080921.04E-058.92E-058.92E-05DownE2F transcription factor 8
A_23_P348169MGC35169-1.011361.12E-059.59E-059.59E-05DownHomo sapiens hypothetical protein MGC35169 (MGC35169), mRNA [NM_152324]
A_23_P209241THC2093007-1.126351.13E-059.64E-059.64E-05DownUnknown
A_23_P377284TGFA-1.691571.16E-059.83E-059.83E-05DownHomo sapiens transforming growth factor, alpha (TGFA), mRNA [NM_003236]
A_23_P19532DEF6-1.134551.19E-050.0001010.000101DownHomo sapiens differentially expressed in FDCP 6 homolog (mouse) (DEF6), mRNA [NM_022047]
A_23_P204469PLA2G1B- 1.434161.2E-050.0001010.000101DownHomo sapiens phospholipase A2, group IB (pancreas) (PLA2G1B), mRNA [NM_000928]
A_23_P34375TCEA3- 1.154721.25E-050.0001050.000105DownHomo sapiens transcription elongation factor A (SII), 3 (TCEA3), mRNA [NM_003196]
A_23_P258862PDCD4- 1.022291.32E-050.000110.00011DownHomo sapiens programmed cell death 4 (neoplastic transfor- mation inhibitor) (PDCD4), transcript variant 2, mRNA [NM_145341]
A_23_P167256PHF17- 1.004591.39E-050.0001150.000115DownHomo sapiens cDNA: FLJ22479 fis, clone HRC10831. [AK026132]
A_23_P133445GZMA-1.467571.45E-050.0001190.000119DownHomo sapiens granzyme A (granzyme 1, cytotoxic T-lym- phocyte-associated serine esterase 3) (GZMA), mRNA [NM_006144]
A_23_P205746EML1- 1.025661.45E-050.000120.00012DownHomo sapiens echinoderm microtubule-associated protein- like 1 (EML1), transcript variant 2, mRNA [NM_004434]
A_23_P145694ASNS-0.926341.45E-050.000120.00012DownHomo sapiens asparagine synthetase (ASNS), transcript vari- ant 2, mRNA [NM_001673]
A_23_P205273PPP1R13B-1.081141.48E-050.0001210.000121DownHomo sapiens protein phosphatase 1, regulatory (inhibitor) subunit 13B (PPP1R13B), mRNA [NM_015316]
A_23_P37704CDT1- 1.080281.57E-050.0001270.000127DownHomo sapiens DNA replication factor (CDT1), mRNA [NM_030928]
Table 1 (continued)
Agiliant IdGene symbolLogFCP valueFDRT valueRegulationGene name
A_23_P358917CYP3A7-1.9041.62E-050.0001310.000131DownHomo sapiens cytochrome P450, family 3, subfamily A, polypeptide 7 (CYP3A7), mRNA [NM_000765]
A_23_P93180HIST1H2BC- 1.046441.71E-050.0001370.000137DownHomo sapiens histone 1, H2bc (HIST1H2BC), mRNA [NM_003526]
A_23_P157245MGC9712-1.716041.77E-050.0001410.000141DownHomo sapiens hypothetical protein MGC9712 (MGC9712), mRNA [NM_152689]
A_23_P110122CCNG2-0.910071.98E-050.0001560.000156DownHomo sapiens cyclin G2 (CCNG2), mRNA [NM_004354]
A_23_P35006AMY2B- 1.005772.02E-050.0001580.000158DownHomo sapiens amylase, alpha 2B; pancreatic (AMY2B), mRNA [NM_020978]
A_23_P50517ZNF541-1.120792.13E-050.0001650.000165DownHomo sapiens zinc finger protein 541 (ZNF541), mRNA [NM_032255]
A_23_P168427MGC2463-0.971972.32E-050.0001780.000178DownHomo sapiens hypothetical protein MGC2463 (MGC2463), mRNA [NM_024070]
A_23_P42178HIST1H2BF-1.217432.41E-050.0001840.000184DownHomo sapiens histone 1, H2bf (HIST1H2BF), mRNA [NM_003522]
A_23_P22422PNMA3- 1.014712.49E-050.0001890.000189DownHomo sapiens paraneoplastic antigen MA3 (PNMA3), mRNA [NM_013364]
A_23_P161076CD2-1.125312.49E-050.0001890.000189DownHomo sapiens CD2 antigen (p50), sheep red blood cell receptor (CD2), mRNA [NM_001767]
A_23_P111042HIST1H2BI-1.165912.65E-050.0001990.000199DownHomo sapiens histone 1, H2bi (HIST1H2BI), mRNA [NM_003525]
A_23_P49499ST6GALNAC2-0.924142.67E-050.0002010.000201DownHomo sapiens sialyltransferase 7 ((alpha-N-acetylneu- raminyl-2,3-beta-galactosyl-1,3)-N-acetyl galactosami- nide alpha-2,6-sialyltransferase) B (SIAT7B), mRNA [NM_006456]
A_23_P407565CX3CR1-1.459512.7E-050.0002030.000203DownHomo sapiens chemokine (C-X3-C motif) receptor 1 (CX3CR1), mRNA [NM_001337]
A_23_P108823OSBPL6- 1.535892.74E-050.0002050.000205DownHomo sapiens oxysterol binding protein-like 6 (OSBPL6), transcript variant 2, mRNA [NM_145739]
A_23_P170587SMYD2-0.909573.09E-050.0002260.000226DownHomo sapiens SET and MYND domain containing 2 (SMYD2), mRNA [NM_020197]
A_23_P80048FER1L4- 1.034323.19E-050.0002330.000233DownHomo sapiens cDNA FLJ13459 fis, clone PLACE1003366, weakly similar to Homo sapiens otoferlin (OTOF) mRNA. [AK023521]
A_23_P129204IDH2-1.082053.22E-050.0002350.000235DownHomo sapiens isocitrate dehydrogenase 2 (NADP+), mito- chondrial (IDH2), mRNA [NM_002168]
A_23_P21260U96396-1.066053.29E-050.0002380.000238DownHomo sapiens anti-streptococcal/anti-myosin immunoglobu- lin kappa light chain variable region mRNA, partial cds. [U96396]
A_23_P30776HIST1H2BE-1.154943.32E-050.000240.00024DownHomo sapiens histone 1, H2be (HIST1H2BE), mRNA [NM_003523]
A_23_P8807CYP3A5-2.101123.62E-050.0002590.000259DownHomo sapiens cytochrome P450, family 3, subfamily A, polypeptide 5 (CYP3A5), mRNA [NM_000777]
A_23_P90510C19orf32-0.931053.74E-050.0002670.000267DownHomo sapiens chromosome 19 open reading frame 32 (C19orf32), mRNA [NM_138393]
A_23_P40174MMP9-1.026123.81E-050.0002710.000271DownHomo sapiens matrix metalloproteinase 9 (gelatinase B, 92 kDa gelatinase, 92 kDa type IV collagenase) (MMP9), mRNA [NM_004994]
A_23_P207521COL1A1-2.326253.84E-050.0002730.000273DownHomo sapiens collagen, type I, alpha 1 (COL1A1), mRNA [NM_000088]
A_23_P135184RALGDS-1.037093.87E-050.0002740.000274DownHomo sapiens ral guanine nucleotide dissociation stimulator (RALGDS), mRNA [NM_006266]
A_23_P330581MGC14816-1.64983.91E-050.0002770.000277DownHomo sapiens hypothetical protein MGC14816 (MGC14816), mRNA [NM_144620]
A_23_P325040TMPO- 1.054873.97E-050.0002810.000281DownHomo sapiens thymopoietin (TMPO), mRNA [NM_003276]
A_23_P134204NYD-SP18- 1.048854.07E-050.0002860.000286DownHomo sapiens testes development-related NYD-SP18 (NYD- SP18), mRNA [NM_032599]
A_23_P112531EEIG1-0.904344.12E-050.0002890.000289DownHomo sapiens early estrogen-induced gene 1 protein (EEIG1), mRNA [NM_203305]
A_23_P93348LTB-1.268614.4E-050.0003060.000306DownHomo sapiens lymphotoxin beta (TNF superfamily, member 3) (LTB), transcript variant 1, mRNA [NM_002341]
Table 1 (continued)
Agiliant IdGene symbolLogFCP valueFDRT valueRegulationGene name
A_23_P110253KIT-1.039654.51E-050.0003120.000312DownHomo sapiens v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT), mRNA [NM_000222]
A_23_P82814FBXO32-0.92124.54E-050.0003140.000314DownHomo sapiens F-box protein 32 (FBXO32), transcript variant 1, mRNA [NM_058229]
A_23_P167168IGJ-1.202314.65E-050.0003210.000321DownHomo sapiens immunoglobulin J polypeptide, linker protein for immunoglobulin alpha and mu polypeptides (IGJ), mRNA [NM_144646]
A_23_P253002IQGAP2-0.914084.95E-050.0003380.000338DownHomo sapiens IQ motif-containing GTPase activating protein 2 (IQGAP2), mRNA [NM_006633]
A_23_P20423RHOBTB2-0.983864.96E-050.0003380.000338DownHomo sapiens Rho-related BTB domain containing 2 (RHOBTB2), mRNA [NM_015178]
A_23_P503042F11R-0.891755.26E-050.0003560.000356DownHomo sapiens F11 receptor (F11R), transcript variant 4, mRNA [NM_144503]
A_23_P302672DDIT4L-1.099495.37E-050.0003630.000363DownHomo sapiens DNA-damage-inducible transcript 4-like (DDIT4L), mRNA [NM_145244]
A_23_P203833HRB2- 1.461255.55E-050.0003730.000373DownHuman clone A9A2BRB2 (CAC)n/(GTG)n repeat-contain- ing mRNA. [U00943]
A_23_P126075KCNK1-1.364375.9E-050.0003920.000392DownHomo sapiens potassium channel, subfamily K, member 1 (KCNK1), mRNA [NM_002245]
A_23_P257516MICA-1.07735.92E-050.0003930.000393DownHomo sapiens MHC class I polypeptide-related sequence A (MICA), mRNA [NM_000247]
A_23_P389281HOXA13-1.237376.21E-050.000410.00041DownHomo sapiens homeo box A13 (HOXA13), mRNA [NM_000522]
A_23_P210763JAG1-1.210526.26E-050.0004120.000412DownHomo sapiens jagged 1 (Alagille syndrome) (JAG1), mRNA [NM_000214]
A_23_P209179#N/A-1.195436.74E-050.0004390.000439DownUnknown
A_23_P120594ACAS2L- 1.403946.86E-050.0004450.000445DownHomo sapiens acetyl-Coenzyme A synthetase 2 (AMP forming)-like (ACAS2L), nuclear gene encoding mito- chondrial protein, mRNA [NM_032501]
A_23_P69586FAT-0.944986.89E-050.0004460.000446DownHomo sapiens FAT tumor suppressor homolog 1 (Dros- ophila) (FAT), mRNA [NM_005245]
A_23_P134764LY6D-0.972946.92E-050.0004470.000447DownHomo sapiens lymphocyte antigen 6 complex, locus D (LY6D), mRNA [NM_003695]
A_23_P385126DEPDC7-1.004857.08E-050.0004560.000456DownDEP domain containing 7
A_23_P97700TXNIP-0.952267.51E-050.000480.00048DownHomo sapiens thioredoxin interacting protein (TXNIP), mRNA [NM_006472]
A_23_P208880UHRF1-1.033777.66E-050.0004880.000488DownHomo sapiens ubiquitin-like, containing PHD and RING finger domains, 1 (UHRF1), mRNA [NM_013282]
A_23_P18452CXCL9- 1.323497.74E-050.0004920.000492DownHomo sapiens chemokine (C-X-C motif) ligand 9 (CXCL9), mRNA [NM_002416]
A_23_P7642SPARC-1.37488.28E-050.000520.00052DownHomo sapiens secreted protein, acidic, cysteine-rich (oste- onectin) (SPARC), mRNA [NM_003118]
A_23_P57779CLDN1-1.561658.45E-050.000530.00053DownHomo sapiens claudin 1 (CLDN1), mRNA [NM_021101]
A_23_P82449DFNA5-1.460319.32E-050.0005790.000579DownHomo sapiens deafness, autosomal dominant 5 (DFNA5), mRNA [NM_004403]
A_23_P92710RHOBTB3-1.127919.35E-050.000580.00058DownHomo sapiens Rho-related BTB domain containing 3 (RHOBTB3), mRNA [NM_014899]
A_23_P434398C6orf198- 1.469659.38E-050.0005820.000582DownHomo sapiens mRNA; cDNA DKFZp451F022 (from clone DKFZp451F022); complete cds. [AL834248]
A_23_P218523C19orf28-0.963899.86E-050.0006060.000606DownHomo sapiens clone PP3501 unknown mRNA. [AF218008]
A_23_P47034HHEX-1.091460.0001020.0006210.000621DownHomo sapiens hematopoietically expressed homeobox (HHEX), mRNA [NM_002729]
A_23_P422851CABLES1-0.8990.0001030.0006280.000628DownHomo sapiens Cdk5 and Abl enzyme-substrate 1 (CABLES1), mRNA [NM_138375]
A_23_P215566AHR-0.982370.0001060.0006440.000644DownHomo sapiens aryl hydrocarbon receptor (AHR), mRNA [NM_001621]
A_23_P52610DDB2-1.165760.0001070.0006520.000652DownHomo sapiens damage-specific DNA binding protein 2, 48 kDa (DDB2), mRNA [NM_000107]
A_23_P134910GGH- 1.244490.0001080.0006540.000654DownHomo sapiens gamma-glutamyl hydrolase (conjugase, folylpolygammaglutamyl hydrolase) (GGH), mRNA [NM_003878]
Table 1 (continued)
Agiliant IdGene symbolLogFCP valueFDRT valueRegulationGene name
A_23_P19379HIST1H2BD- 1.045730.0001170.0007010.000701DownHomo sapiens histone 1, H2bd (HIST1H2BD), transcript variant 1, mRNA [NM_021063]
A_23_P40470H2BFS-0.927930.0001180.0007060.000706DownHomo sapiens H2B histone family, member S (H2BFS), mRNA [NM_017445]
A_23_P94380C9orf58- 1.826090.0001180.0007060.000706DownHomo sapiens chromosome 9 open reading frame 58 (C9orf58), transcript variant 1, mRNA [NM_031426]
A_23_P93260PRSS16-0.997510.0001260.0007480.000748DownHomo sapiens protease, serine, 16 (thymus) (PRSS16), mRNA [NM_005865]
A_23_P259692PSAT1- 1.247350.0001260.0007490.000749DownHomo sapiens phosphoserine aminotransferase 1 (PSAT1), transcript variant 1, mRNA [NM_058179]
A_23_P96115HLA-DQB1-0.996890.0001280.0007570.000757DownHuman MHC class II HLA-DQ-beta (DR2-DQw1/DR4 DQw3) mRNA, complete cds, clone ROF2D. [M20432]
A_23_P158096COL27A1-1.190080.0001520.0008770.000877DownHomo sapiens cDNA FLJ11895 fis, clone HEMBA1007301, weakly similar to COLLAGEN ALPHA 1(III) CHAIN. [AK021957]
A_23_P154605SULF2- 1.728290.000170.0009660.000966DownHomo sapiens sulfatase 2 (SULF2), transcript variant 1, mRNA [NM_018837]
A_23_P120902LGALS2-0.917180.0001720.0009760.000976DownHomo sapiens lectin, galactoside-binding, soluble, 2 (galec- tin 2) (LGALS2), mRNA [NM_006498]
A_23_P133851HIST1H2BJ-1.144850.0001930.0010750.001075DownHomo sapiens histone 1, H2bj (HIST1H2BJ), mRNA [NM_021058]
A_23_P207999PMAIP1- 1.097130.0001990.0011050.001105DownHomo sapiens phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1), mRNA [NM_021127]
A_23_P20864ANGPTL2-0.952580.0002010.0011140.001114DownHomo sapiens angiopoietin-like 2 (ANGPTL2), mRNA [NM_012098]
A_23_P138985CD3D-1.03220.0002090.0011550.001155DownHomo sapiens CD3D antigen, delta polypeptide (TiT3 com- plex) (CD3D), mRNA [NM_000732]
A_23_P91850IL20RB-1.299460.0002230.0012240.001224DownInterleukin 20 receptor subunit beta
A_23_P204170TMPO-1.04230.0002280.0012440.001244DownHSU09086 thymopoietin alpha {Homo sapiens; }, partial (16%) [THC2199856]
A_23_P211141DSCAM-1.152840.0002340.0012740.001274DownHomo sapiens Down syndrome cell adhesion molecule (DSCAM), transcript variant 1, mRNA [NM_001389]
A_23_P111054HIST1H2BB-0.981910.0002580.0013880.001388DownHomo sapiens histone 1, H2bb (HIST1H2BB), mRNA [NM_021062]
A_23_P333029ERICH5- 1.248620.000260.0013960.001396DownGlutamate rich 5
A_23_P21912LOC58489-0.930440.0002620.0014060.001406DownHomo sapiens hypothetical protein from EUROIMAGE 588495, mRNA (cDNA clone IMAGE:30346383), partial cds. [BC059401]
A_23_P206884BE769278- 1.285970.0002650.0014190.001419DownBE769278 PM4-FT0027-050600-001-a03 FT0027 Homo sapiens cDNA, mRNA sequence [BE769278]
A_23_P163467CCDC9B- 1.076590.0002820.0014960.001496DownCoiled-coil domain containing 9B
A_23_P39885DPP4- 1.390590.0002940.0015470.001547DownHomo sapiens dipeptidylpeptidase 4 (CD26, adenosine deaminasecomplexing protein 2) (DPP4), mRNA [NM_001935]
A_23_P393051TMPO-0.95480.0003060.0016030.001603DownHomo sapiens hypothetical protein FLJ34633 (FLJ34633), mRNA [NM_152365]
A_23_P216361COL14A1-1.119320.0003060.0016030.001603DownHomo sapiens collagen, type XIV, alpha 1 (undulin) (COL14A1), mRNA [NM_021110]
A_23_P83736ING1L-0.954050.0003220.0016750.001675DownHomo sapiens inhibitor of growth family, member 1-like (ING1L), mRNA [NM_001564]
A_23_P251662SMS-0.894410.0003590.0018360.001836DownHomo sapiens spermine synthase (SMS), mRNA [NM_004595]
A_23_P165968SEMG1-1.240630.0003630.0018570.001857DownHomo sapiens semenogelin I (SEMG1), transcript variant 1, mRNA [NM_003007]
A_23_P142527COL3A1- 1.849850.0004030.0020350.002035DownHomo sapiens collagen, type III, alpha 1 (Ehlers-Danlos syn- drome type IV, autosomal dominant) (COL3A1), mRNA [NM_000090]
A_23_P158817AF272774-1.816680.0004240.002120.00212DownHomo sapiens factor VII active site mutant immunoconju- gate mRNA, complete cds. [AF272774]
A_23_P162668CPM- 1.005390.0004240.0021220.002122DownHomo sapiens carboxypeptidase M (CPM), transcript variant 1, mRNA [NM_001874]
Table 1 (continued)
Agiliant IdGene symbolLogFCP valueFDRT valueRegulationGene name
A_23_P42407HLA-DRB4-0.942760.0004380.0021760.002176DownHomo sapiens major histocompatibility complex, class II, DR beta 4 (HLA-DRB4), mRNA [NM_021983]
A_23_P217797DDX3Y-1.159540.000470.0023150.002315DownHomo sapiens DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, Y-linked (DDX3Y), mRNA [NM_004660]
A_23_P140884TUBB7P- 1.022910.0005140.0024940.002494DownTubulin beta 7 pseudogene
A_23_P23664PALMD-0.925560.000520.0025140.002514DownHomo sapiens palmdelphin (PALMD), mRNA [NM_017734]
A_23_P24674OR8U1-0.954130.0005460.0026220.002622DownHomo sapiens olfactory receptor, family 8, subfamily U, member 1 (OR8U1), mRNA [NM_001005204]
A_23_P106925CHST6-1.338510.00060.0028490.002849DownHomo sapiens carbohydrate (N-acetylglucosamine 6-O) sulfotransferase 6 (CHST6), mRNA [NM_021615]
A_23_P116183BCDO2-1.328760.0006250.0029440.002944DownHomo sapiens beta-carotene dioxygenase 2 (BCDO2), mRNA [NM_031938]
A_23_P87879CD69- 1.004740.0006360.0029880.002988DownHomo sapiens CD69 antigen (p60, early T-cell activation antigen) (CD69), mRNA [NM_001781]
A_23_P56746FAP-1.671650.0006640.0030990.003099DownHomo sapiens fibroblast activation protein, alpha (FAP), mRNA [NM_004460]
A_23_P8571SRCRB4D-1.147650.0006910.0032030.003203DownHomo sapiens scavenger receptor cysteine-rich domain containing, group B (4 domains) (SRCRB4D), mRNA [NM_080744]
A_23_P148088FGG-2.842260.0006930.0032060.003206DownHomo sapiens fibrinogen, gamma polypeptide (FGG), tran- script variant gamma-B, mRNA [NM_021870]
A_23_P205111POSTN-1.639120.0007160.00330.0033DownHomo sapiens periostin, osteoblast specific factor (POSTN), mRNA [NM_006475]
A_23_P392384C9orf58-1.434720.0007920.0035830.003583DownHomo sapiens chromosome 9 open reading frame 58 (C9orf58), transcript variant 1, mRNA [NM_031426]
A_23_P59470BC038972- 1.040690.000830.0037350.003735DownHomo sapiens, Similar to hypothetical protein, MNCb-3350, clone IMAGE:5216914, mRNA. [BC038972]
A_23_P60599UGT1A6-1.11180.0009290.0040950.004095DownHomo sapiens UDP glycosyltransferase 1 family, polypeptide A6 (UGT1A6), transcript variant 1, mRNA [NM_001072]
A_23_P108676FLJ13391-0.971970.0009410.0041390.004139DownHomo sapiens hypothetical protein FLJ13391 (FLJ13391), mRNA [NM_032181]
A_23_P102058MATN3-0.993670.0009840.0042920.004292DownHomo sapiens matrilin 3 (MATN3), mRNA [NM_002381]
A_23_P73632NR0B1- 1.745740.0010260.0044510.004451DownHomo sapiens nuclear receptor subfamily 0, group B, mem- ber 1 (NR0B1), mRNA [NM_000475]
A_23_P81898UBD-1.684760.0011050.0047240.004724DownHomo sapiens ubiquitin D (UBD), mRNA [NM_006398]
A_23_P54546TPSAB1-0.921430.0011360.0048410.004841DownHomo sapiens tryptase alpha/beta 1 (TPSAB1), mRNA [NM_003294]
A_23_P23996MAT1A-1.262780.0012020.005080.00508DownHomo sapiens methionine adenosyltransferase I, alpha (MAT1A), mRNA [NM_000429]
A_23_P74012SPRR1A-1.201880.0012530.0052610.005261DownHomo sapiens small proline-rich protein 1A (SPRR1A), mRNA [NM_005987]
A_23_P103703HSPB7-0.914140.0013980.0057740.005774DownHomo sapiens heat shock 27 kDa protein family, member 7 (cardiovascular) (HSPB7), mRNA [NM_014424]
A_23_P320242KIAA1324L-0.950680.0014150.0058350.005835DownKIAA1324 like
A_23_P120819IGLL1-0.947690.0014890.0060820.006082DownHomo sapiens immunoglobulin lambda-like polypeptide 1 (IGLL1), transcript variant 1, mRNA [NM_020070]
A_23_P128918LGALS3-0.975970.0015180.0061790.006179DownHomo sapiens lectin, galactoside-binding, soluble, 3 (galec- tin 3) (LGALS3), mRNA [NM_002306]
A_23_P137478THC2046518-0.896650.0015780.0063820.006382DownSP2E_HUMAN (P22531) Small proline-rich protein 2E (SPR-2E) (Small proline-rich protein II) (SPR-II), com- plete [THC2046518]
A_23_P218128IGHM- 1.426760.0018820.0073610.007361DownHomo sapiens immunoglobulin heavy constant mu, mRNA (cDNA clone MGC:52291 IMAGE:4765763), complete cds. [BC041037]
A_23_P30254PLK2-0.947950.0019710.0076420.007642DownHomo sapiens polo-like kinase 2 (Drosophila) (PLK2), mRNA [NM_006622]
A_23_P41917HOMER1-0.946460.0020630.0079140.007914DownHomo sapiens homer homolog 1 (Drosophila) (HOMER1), mRNA [NM_004272]
A_23_P82651NPTX2-1.739650.0024160.0089840.008984DownHomo sapiens neuronal pentraxin II (NPTX2), mRNA [NM_002523]
Table 1 (continued)
Agiliant IdGene symbolLogFCP valueFDRT valueRegulationGene name
A_23_P91669PIB5PA-0.903110.0024280.0090130.009013DownHomo sapiens phosphatidylinositol (4,5) bisphosphate 5-phosphatase, A (PIB5PA), transcript variant 1, mRNA [NM_014422]
A_23_P25194HRK-1.175070.0024590.0090980.009098DownHomo sapiens harakiri, BCL2 interacting protein (contains only BH3 domain) (HRK), mRNA [NM_003806]
A_23_P60848AB064167-1.111060.0025650.0094230.009423DownHomo sapiens IGL mRNA for immunoglobulin lambda light chain VLJ region, partial cds, clone:L27. [AB064167]
A_23_P84060HNT-0.938160.0027910.010090.01009DownHomo sapiens neurotrimin (HNT), mRNA [NM_016522]
A_23_P23221GADD45A-1.073020.0033070.0115440.011544DownHomo sapiens growth arrest and DNA-damage-inducible, alpha (GADD45A), mRNA [NM_001924]
A_23_P16254KLK1- 1.44220.0033950.01180.0118DownHomo sapiens kallikrein 1, renal/pancreas/salivary (KLK1), mRNA [NM_002257]
A_23_P259314RPS4Y1-2.414450.0035890.012340.01234DownHomo sapiens ribosomal protein S4, Y-linked 1 (RPS4Y1), mRNA [NM_001008]
A_23_P435390#N/A-0.898350.0036070.0123910.012391DownUnknown
A_23_P154526GRB14-1.02910.0036970.0126250.012625DownHomo sapiens growth factor receptor-bound protein 14 (GRB14), mRNA [NM_004490]
A_23_P123853CCL19-1.089990.0037030.0126420.012642DownHomo sapiens chemokine (C-C motif) ligand 19 (CCL19), mRNA [NM_006274]
A_23_P209925FN1-1.127650.0038420.0130370.013037DownHomo sapiens fibronectin 1 (FN1), transcript variant 3, mRNA [NM_002026]
A_23_P324384RPS4Y2-2.032690.0043440.0143690.014369DownHomo sapiens ribosomal protein S4, Y-linked 2 (RPS4Y2), mRNA [NM_138963]
A_23_P34518FABP3-0.94770.0055230.0174750.017475DownHomo sapiens fatty acid-binding protein 3, muscle and heart (mammary-derived growth inhibitor) (FABP3), mRNA [NM_004102]
A_23_P206359CDH1- 1.474060.0055410.0175280.017528DownHomo sapiens cadherin 1, type 1, E-cadherin (epithelial) (CDH1), mRNA [NM_004360]
A_23_P8175PLAGL1-1.243880.0066570.0204480.020448DownHomo sapiens pleiomorphic adenoma gene-like 1 (PLAGL1), transcript variant 1, mRNA [NM_002656]
A_23_P91230SLPI- 1.546920.0069570.0211830.021183DownHomo sapiens secretory leukocyte protease inhibitor (anti- leukoproteinase) (SLPI), mRNA [NM_003064]
A_23_P67381SULT2A1-1.329340.0072080.0217690.021769DownHomo sapiens sulfotransferase family, cytosolic, 2A, dehydroepiandrosterone (DHEA)-preferring, member 1 (SULT2A1), mRNA [NM_003167]
A_23_P33196COL5A2-0.891840.0076080.0226960.022696DownHomo sapiens collagen, type V, alpha 2 (COL5A2), mRNA [NM_000393]
A_23_P122445HIST1H1C-1.194280.0077950.0231220.023122DownHomo sapiens histone 1, H1c (HIST1H1C), mRNA [NM_005319]
A_23_P133862C6orf194-0.965030.0082250.0240670.024067DownHomo sapiens chromosome 6 open reading frame 194 (C6orf194), mRNA [NM_001007531]
A_23_P170713#N/A-1.103820.009120.0261410.026141DownUnknown
A_23_P162916SERPINA3- 1.397240.0099860.0281550.028155DownHomo sapiens serine (or cysteine) proteinase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 3 (SER- PINA3), mRNA [NM_001085]
A_23_P136724NMRAL2P-0.992780.0104840.0292330.029233DownNmrA like redox sensor 2, pseudogene
A_23_P169437LCN2-0.917330.0138820.0364610.036461DownHomo sapiens lipocalin 2 (oncogene 24p3) (LCN2), mRNA [NM_005564]
A_23_P340088PRSS8-0.893660.0142990.0373060.037306DownHomo sapiens protease, serine, 8 (prostasin) (PRSS8), mRNA [NM_002773]
A_23_P259065PDE8B-0.90670.015450.0397550.039755DownHomo sapiens phosphodiesterase 8B (PDE8B), mRNA [NM_003719]
A_23_P34345VCAM1-1.143330.0164860.0419880.041988DownHomo sapiens vascular cell adhesion molecule 1 (VCAM1), transcript variant 1, mRNA [NM_001078]
A_23_P25030RODH-1.300110.0169470.0429780.042978DownHomo sapiens 3-hydroxysteroid epimerase (RODH), mRNA [NM_003725]
A_23_P69171SUCNR1-1.075450.0169870.0430480.043048DownHomo sapiens succinate receptor 1 (SUCNR1), mRNA [NM_033050]
Fig. 3 Heat map of gene expres- sion (Upregulated genes). The color key represents the logFC of DEGs. FC, fold change (A1,A2, A3, A4, A5, A6, A7, A8, A9,A10, A11, A12, A13, A14, A15 = adrenocortical carcinoma samples, B1,B2, B3, B4, B5,B6, B7, B8, B9,B10, B11, B12, B13, B14, B15=nor- mal whole adrenal gland samples)

Color Key and Histogram

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PPI network and sub-modules analysis

We constructed a PPI network to further explore the interac- tion between the common DEGs (up and down regulated) by using PINA database and Cytoscape. A total of 5050 nodes and 9534 edges were included in the PPI networks (up regulated) (Fig. 5). The hub genes with highest node degree in this PPI network such as YWHAZ (degree=805), HSPA5 (degree =394), STAT3 (degree=213), APOE (degree = 183), and GRK5 (degree =175) are listed in Table 6. A total of 5146 nodes and 11,499 edges were included in the PPI networks (down regulated) (Fig. 6). The hub genes with highest node degree in this PPI net- work such as FN1 (degree=1012), VCAM1 (degree=671), UBD (degree =664), BARD1 (degree =252), and TK1 (degree = 169) are listed in Table 6. R square = 0.761 and correlation coefficient = 0.967 for node degree (up regu- lated) (Fig. 7a), meanwhile R square =0.761 and correla- tion coefficient =0.978 for node degree (down regulated) (Fig. 7b). The hub genes with highest betweenness in PPI network for up regulated genes such as YWHAZ (between- ness =0.26018915), HSPA5 (betweenness=0.10211544), STAT3 (betweenness = 0.05179592), TH (between- ness =0.05146886), and CD83 (betweenness =0.04395976)

are listed in Table 6. R square = 0.602 and correlation coefficient = 0.105 for betweenness (Fig. 8a). The hub genes with highest stress in PPI network for up regulated genes such as YWHAZ (stress = 110811588), HSPA5 (stress =43035116), ICAM1 (stress=27529814), HOXB2 (stress =23,027,092), and STAT3 (stress =22,678,172) are listed in Table 6. R square = 0.001 and correlation coeffi- cient=0.111 for stress (Fig. 8b). The hub genes with high- est closeness in PPI network for up regulated genes such as YWHAZ (closeness = 0.40211725), HSPA5 (close- ness = 0.38225204), NR4A1 (closeness =0.36144752), IRS1 (closeness = 0.35719883), and MAP3K5 (close- ness =0.35502372) are listed in Table 6. R square =0.186 and correlation coefficient=0.338 for closeness (Fig. 8c). The hub genes with lowest clustering coefficient in PPI net- work for up regulated genes such as CRLF1 (clustering coef- ficient=0), CRH (clustering coefficient=0), ARHGAP18 (clustering coefficient=0), FJX1 (clustering coefficient=0), and FMO3 (clustering coefficient =0) are listed in Table 6. R square =0.447 and correlation coefficient =0.686 for clustering coefficient (Fig. 8d). The hub genes with high- est betweenness in PPI network for down regulated genes such as FN1 (betweenness=0.24710836), UBD (between- ness =0.14892195), VCAM1 (betweenness=0.11467148),

Fig. 4 Heat map of gene expression (Down-regulated genes). The color key represents the logFC of DEGs. FC, fold change (A1,A2, A3, A4, A5, A6, A7, A8, A9,A10, A11, A12, A13, A14, A15= adreno- cortical carcinoma samples, B1,B2, B3, B4, B5,B6, B7, B8, B9,B10, B11, B12, B13, B14, B15 = normal whole adrenal gland samples)

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BARD1 (betweenness=0.05118512), and TK1 (between- ness =0.04488624) are listed in Table 6. R square =0.574 and correlation coefficient =0.109 for betweenness (Fig. 9a). The hub genes with highest stress in PPI network for down regulated genes such as FN1 (stress =358,695,218), UBD (stress=286,343,980), VCAM1 (stress=222,971,648), SLPI (stress =46,566,718), and BARD1 (stress=43,410,948) are listed in Table 6. R square =0.011 and correlation coeffi- cient =0.090 for stress (Fig. 9b). The hub genes with high- est closeness in PPI network for down regulated genes such as FN1 (closeness =0.42073523), VCAM1 (close- ness =0.39252408), MCM3 (closeness=0.39092723), PHGDH (closeness =0.38138386), and MCM6 (close- ness =0.3806143) are listed in Table 6. R square =0.198 and correlation coefficient=0.293 for closeness (Fig. 9c). The hub genes with lowest clustering coefficient in PPI net- work for down regulated genes such as CYP3A5 (cluster- ing coefficient=0), POPDC2 (clustering coefficient =0), PNLIPRP2 (clustering coefficient=0), KIAA1407 (cluster- ing coefficient=0), and CX3CR1 (clustering coefficient=0) are listed in Table 6. R square = 0.663 and correlation coef- ficient=0.810 for clustering coefficient (Fig. 9d).

Subsequently, we performed module analysis of the whole network by the PEWCC1 plug-in. A total of 773

modules were obtained from the PPI network (up regu- lated). The four most significant modules were selected in this PPI network such as module 6, module 30, module 37, and module 55 (Fig. 10). Module 6 had 48 nodes and 119 edges. Hub genes in this modules such as YWHAZ (degree = 805), GRK5 (degree =175), and NOLC1 (degree =99). Module 30 had 10 nodes and 19 edges. Hub genes in this modules such as ID2 (degree =46), STAT3 (degree=213), HES1 (degree=43), NR4A1 (degree=116), ZNF331 (degree=11), and YWHAZ (degree=805). Mod- ule 37 had 8 nodes and 22 edges. Hub genes in this mod- ules such as APOE (degree =183), PLAT (degree=34), C1S (degree =12), SERPING1 (degree =137), HP (degree = 160), APOC1 (degree =151), and SH3BP5 (degree = 142). Module 55 had 7 nodes and 12 edges. Hub genes in this modules such as STAT1 (degree=174), IPO7 (degree =47), and HSPA4L (degree =40). Mean- while, total of 923 modules were obtained from the PPI network (down regulated). The four most significant mod- ules were selected in this PPI network such as module 2, module 8, module 10, and module 27 (Fig. 11). Module 2 had 69 nodes and 239 edges. Hub genes in this modules such as VCAM1 (degree =671), FN1 (degree =1012), MCM3 (degree=126), MCM2 (degree=110), and MCM6

Table 2 The enriched pathway terms of the upregulated differentially-expressed genes
Pathway IDPathway nameLogPGene countGenes
BIOCYC
142238Catecholamine biosynthesis3.32936167702DDC,PNMT
545304Glucocorticoid biosynthesis2.86792826502CYP17A1,CYP21A2
545305Mineralocorticoid biosynthesis2.86792826502CYP11B2,CYP21A2
907943Superpathway of steroid hormone biosynthesis2.73075979603CYP11B2,CYP17A1,CYP21A2
545352Acetone degradation I (to methylglyoxal)1.92883599102ADH1B,AKR1B1
545295Retinoate biosynthesis I1.9288359910ALDH1A1,ALDH1A3
545354Noradrenaline and adrenaline degradation1.82583356502ADH1B,PNMT
142437Nicotine degradation IV1.73505451102AOX1,FMO3
142427Sulfate activation for sulfonation1.3721886301PAPSS2
142362Lysine degradation I (saccharopine pathway)1.3721886301AASS
545298Thyroid hormone biosynthesis1.3721886301CTSD
KEGG
1272485Aldosterone synthesis and secretion1012CYP11A1,CYP11B2,CYP21A2,HSD3B1,HSD3B2,KCNK3,LDLR,MC2 R,NR4A1,NR4A2,PRKD3,SCARB1
82959Tyrosine metabolism1010ADH1A,ADH1B,ADH1C,ALDH1A3,AOC3,AOX1,DBH,DDC,PNMT ,TH
413357Catecholamine biosynthesis, tyrosine => dopamine => noradrena- line => adrenaline5.99261888604DBH,DDC,PNMT,TH
212237Mineral absorption5.93540069909ATP1B3,HEPH,MT1A,MT1B,MT1E,MT1F,MT1G,MT1H,MT1X
83032Drug metabolism-cytochrome P4505.65326044110ADH1A,ADH1B,ADH1C,ALDH1A3,AOX1,FMO2,FMO3,GSTA4,GST T2,MGST1
413396Steroid hormone biosynthesis, cholesterol =>prognenolone => proges- terone5.00125181503CYP11A1,HSD3B1,HSD3B2
413383C19/C18-Steroid hormone biosynthesis, pregnenolone =>androstenedi- one =>estrone4.41561707103CYP17A1,HSD3B1,HSD3B2
790011Ovarian steroidogenesis4.05766367507CYP11A1,CYP17A1,HSD3B1,HSD3B2,LDLR,PLA2G4A,SCARB1
413395C21-Steroid hormone biosynthesis, progesterone => cortisol/cortisone3.73060541203CYP11B2,CYP17A1,CYP21A2
812256TNF signaling pathway3.28793697309CCL2,CEBPB,CXCL1,CXCL2,ICAM1,IL6,JUNB,MAP3K5,SOCS3
83093Adipocytokinesignaling pathway1.792970322( 05IRS1,NPY,PCK1,SOCS3,STAT3
Pathway interaction database
137932IL6-mediated signaling events4.49342480207CEBPB,CEBPD,IL6,JUNB,SOCS3,STAT1,STAT3
138000IL23-mediated signaling events3.91264548106CCL2,CXCL1,IL6,SOCS3,STAT1,STAT3
138006ATF-2 transcription factor network3.78943676507DUSP5,HES1,IL6,JUNB,PDGFRA,SOCS3,TH
169349Validated transcriptional targets of AP1 family members Fra1 and Fra23.13632510605CCL2,DCN,GJA1,IL6,JUNB
138045HIF-1-alpha transcription factor network1.89692213205ABCB1,ADM,CXCL12,ID2,NDRG1
137911FOXA2 and FOXA3 transcription factor networks1.8436628304ALAS1,CEBPB,CEBPD,PCK1
Table 2 (continued)
Pathway IDPathway nameLogPGene countGenes
137929IL27-mediated signaling events1.75411228103IL6,STAT1,STAT3
137945amb2 Integrin signaling1.71604624504HP,ICAM1,IL6,PLAT
138017Signaling events mediated by PTP1B1.65718500804CDH2,IRS1,SOCS3,STAT3
137976IL2-mediated signaling events1.60126164604IRS1,SOCS3,STAT1,STAT3
138020Class I PI3K signaling events mediated by Akt1.44621804803CASP9,MAP3K5, YWHAZ
REACTOME
1339158Metallothioneins bind metals1007MT1A,MT1B,MT1E,MT1F,MT1G,MT1H,MT1X
1270046Metabolism of steroid hormones1009AKR1B1,CYP11A1,CYP11B2,CYP17A1,CYP21A2,FDX1,HSD3B1,HS D3B2,STARD6
1339157Response to metal ions1007MT1A,MT1B,MT1E,MT1F,MT1G,MT1H,MT1X
1270190Phase 1-functionalization of compounds1015AADAC,ADH1A,ADH1B,ADH1C,ALDH1A1,AOC3,CYP11A1,CYP11 B2,CYP17A1,CYP21A2,CYP26B1,CYP4B1,FDX1,FMO2,FMO3
1270189Biological oxidations1023AADAC,ADH1A,ADH1B,ADH1C,ALDH1A1,AOC3,AS3MT,CYP11A 1,CYP11B2,CYP17A1,CYP21A2,CYP26B1,CYP4B1,FDX1,FMO2,F MO3,GCLM,GSTA4,GSTT2,MAT2A,MGST1,PAPSS2,TPMT
1270176Catecholamine biosynthesis1004DBH,DDC,PNMT,TH
1270048Glucocorticoid biosynthesis1005CYP11B2,CYP17A1,CYP21A2,HSD3B1,HSD3B2
1270049Mineralocorticoid biosynthesis5.52293803704CYP11B2,CYP21A2,HSD3B1,HSD3B2
1270047Pregnenolone biosynthesis4.4063600304AKR1B1,CYP11A1,FDX1,STARD6
1269325Interleukin-6 signaling4.21744047304IL6,SOCS3,STAT1,STAT3
1269318Signaling by Interleukins2.61533622CCL2,CEBPD,CRLF1,CXCL1,CXCL2,DUSP16,DUSP5,FGF23,FGF7,F GF9,ICAM1,IL1R2,IL1RL1,IL6,IRS1,JUNB,PDGFRA,SAA1,SOCS3, STAT1,STAT3, YWHAZ
GenMAPP
MAP00140Steroid hormone metabolism1006CYP11A1,CYP11B2,CYP17A1,CYP21A2,HSD3B1,HSD3B2
MAP00350Tyrosine metabolism1010ADH1A,ADH1B,ADH1C,ALDH1A3,AOC3,AOX1,DBH,DDC,PNMT ,TH
MAP00561Glycerolipid metabolism5.21199042108ADH1A,ADH1B,ADH1C,AKR1B1,ALDH1A1,ALDH3A2,GK,PLA2 G4A
MAP00120Bile acid biosynthesis5.16549219106ADH1A,ADH1B,ADH1C,ALDH1A1,ALDH3A2,SOAT1
MAP00340Histidine metabolism4.28379145905ALDH1A1,ALDH1A3,ALDH3A2,AOC3,DDC
MAP00380Tryptophan metabolism3.37750087606ALDH1A1,ALDH3A2,AOC3,AOX1,CYP4B1,DDC
MAP00071Fatty acid metabolism3.3775008760 06ADH1A,ADH1B,ADH1C,ALDH1A1,ALDH3A2,CYP4B1
MAP00620Pyruvate metabolism3.3277817250AKR1B1,ALDH1A1,ALDH3A2,PC,PCK1
MAP00010Glycolysis Gluconeogenesis3.08692474906ADH1A,ADH1B,ADH1C,ALDH1A1,ALDH1A3,ALDH3A2
MAP00310Lysine degradation2.35254587703AASS,ALDH1A1,ALDH3A2
MAP00480Glutathione metabolism1.95431570703GCLM,GSTT2,MGST1
Table 2 (continued)
Pathway IDPathway nameLogPGene countGenes
MSigDB C2 BIOCARTA (v6.0)
M5889Ensemble of genes encoding extracellular matrix and extracellular matrix-associated proteins4.11927871341ADAMTS1,ADAMTS9,ANGPTL1,ANGPTL4,CCL13,CCL2,CCN3,CR LF1,CTSD,CXCL1,CXCL12,CXCL2,DCN,EFEMP1,FBLN1,FBLN5,F CN2,FGF12,FGF23,FGF7,FGF9,FMOD,GDF15,IGFBP2,IGFBP5,IGF BP6,IL6,LUM,MFAP4,PLAT,S100A8,S100A9,SEMA3B,SEMA6A,SE RPING1,SPOCK3,SPON2,SRPX2,THBS1,TIMP4,TNXB
M4557Biosynthesis of neurotransmitters3.73060541203DBH,PNMT,TH
M5884Ensemble of genes encoding core extracellular matrix including ECM glycoproteins, collagens and proteoglycans3.53361968616CCN3,DCN,EFEMP1,FBLN1,FBLN5,FMOD,IGFBP2,IGFBP5,IGFBP6, LUM,MFAP4,SPOCK3,SPON2,SRPX2,THBS1,TNXB
M3008Genes encoding structural ECM glycoproteins2.97097590512CCN3,EFEMP1,FBLN1,FBLN5,IGFBP2,IGFBP5,IGFBP6,MFAP4,SPO N2,SRPX2,THBS1,TNXB
M18899Repression of pain sensation by the transcriptional regulator DREAM2.52587162503CREM,PRKAR1A,PRKAR2B
M5883Genes encoding secreted soluble factors2.5099109416ANGPTL1,ANGPTL4,CCL13,CCL2,CRLF1,CXCL1,CXCL12,CXCL2, FGF12,FGF23,FGF7,FGF9,GDF15,IL6,S100A8,S100A9
M8066IL22 soluble receptor signaling pathway2.35254587703SOCS3,STAT1,STAT3
M1394GATA3 participate in activating the Th2 cytokine genes expression2.35254587703JUNB,PRKAR1A,PRKAR2B
M6778IL-10 anti-inflammatory signaling pathway2.27509425203IL6,STAT1,STAT3
M3952Cells and molecules involved in local acute inflammatory response2.27509425203C7,ICAM1,IL6
M5885Ensemble of genes encoding ECM-associated proteins including ECM- affilaited proteins, ECM regulators and secreted factors1.70495972125ADAMTS1,ADAMTS9,ANGPTL1,ANGPTL4,CCL13,CCL2,CRLF1,CT SD,CXCL1,CXCL12,CXCL2,FCN2,FGF12,FGF23,FGF7,FGF9,GDF1 5,IL6,PLAT,S100A8,S100A9,SEMA3B,SEMA6A,SERPING1,TIMP4
PantherDB
P05912Dopamine receptor mediated signaling pathway3.94660873107DBH,DDC,EPB41L1,GNAZ,KCNK3,PRKAR2B,TH
P00001Adrenaline and noradrenaline biosynthesis3.54273722805DBH,DDC,PNMT,SLC18A1,TH
P06587Nicotine pharmacodynamics pathway3.4681545505CHRNA3,DDC,EPB41L1,KCNK3,TH
P043725-Hydroxytryptamine degredation2.2027747703ALDH1A1,ALDH1A3,ALDH3A2
P02772Pyruvate metabolism2.04762163502PC,PCK1
P00046Oxidative stress response1.77810645404DUSP16,DUSP5,PLA2G4A,STAT1
P00018EGF receptor signaling pathway1.49249982206MAP3K5,MRAS,PRKD3,STAT1,STAT3,YWHAZ
P05913Enkephalin release1.47959744603CREM,PENK,PRKAR2B
P02778Sulfate assimilation1.3721886301PAPSS2
P00005Angiogenesis1.36877696307CASP9,DLL1,PDGFRA,PLA2G4A,PRKD3,STAT1,STAT3
P00039Metabotropic glutamate receptor group III pathway1.31612290104GRIK1,PRKAR1A,PRKAR2B,SLC1A2
Pathway ontology
PW:0000363Leptin system4.0487193204IRS1,NPY,SOCS3,STAT3
PW:0000238Insulin-like growth factor signaling4.0487193204IGFBP2,IGFBP5,IGFBP6,IRS1
PW:0000052Tyrosine metabolic3.51268330904ALDH3A2,AOX1,DDC,TH
Table 2 (continued)
Pathway IDPathway nameLogPGene countGenes
PW:0000018Parkinson disease3.51268330904CASP9,NR4A2,TH,UCHL1
PW:0000166Nicotinate and nicotinamidemetabolic2.73075979603AOX1,CD38,TESK1
PW:0000482Lipoprotein metabolic2.623715403APOC1,APOE,SCARB1
PW:0000043Pyruvate metabolic2.43727986804AKR1B1,ALDH3A2,PC,PDK4
PW:0000484Altered lipoprotein metabolic2.047621635( 02APOC1,APOE
PW:0000133Selenoamino acid metabolic1.92883599102CTH,MAT2A
PW:0000054Tryptophan metabolic1.90044170602ALDH3A2,AOX1,DDC
PW:0000016Amyotrophic lateral sclerosis disease1.39756509902NEFH,SLC1A2
SMPDB
SMP00012Catecholamine biosynthesis1004DBH,DDC,PNMT,TH
SMP00130Steroidogenesis4.8687162504CYP11A1,CYP17A1,CYP21A2,HSD3B1
SMP00006Tyrosine metabolism3.87631867105ADH1A,DBH,DDC,PNMT,TH
SMP00307Propranolol pathway3.40352261304DBH,DDC,PRKAR1A,TH
SMP00299Betaxolol pathway04DBH,DDC,PRKAR1A,TH
SMP00196Leigh syndrome2.2027747703AKR1B1,PC,PCK1
SMP00060Pyruvate metabolism2.2027747703AKR1B1,PC,PCK1
SMP00068Androgen and estrogen metabolism1.82583356502CYP17A1,HSD3B1
SMP00013Cysteine metabolism1.82583356502CTH,GCLM
SMP00029Selenoamino acid metabolism1.8258335650 02CTH,MAT2A
SMP00375Verapamil pathway1.47285580704ATP1B3,CALD1,EDNRB,KCNQ1

Table 3 The enriched pathway terms of the down-regulated differentially-expressed genes

BIOCYC

Pathway IDPathway nameLogPGenecount Genes
782392Pyrimidine deoxyribonucleosides salvage2.4342771402TK1,TYMS
142235Glutamate removal from folates1.69904773601GGH
142290Spermine biosynthesis1.69904773601SMS
547505Oxidized GTP and dGTP detoxification01NUDT1
782381Pyrimidine deoxyribonucleotides biosynthesis from CTP1.46905898202RRM2,TYMS
782380Pyrimidine deoxyribonucleotides de novo biosynthesis1.46905898202RRM2,TYMS
782391Superpathway of pyrimidine deoxyribonucleoside salvage1.41661325302TK1,TYMS
1108787Protein O-[N-acetyl]-glucosylation1.41092242701OGT
142134Asparagine biosynthesis1.41092242701ASNS
142191GDP-L-fucose biosynthesis II (from L-fucose)1.41092242701FUK
1108783Purine deoxyribonucleosides degradation1.41092242701ADA
KEGG
83122Systemic lupus erythematosus1017HIST1H2BB,HIST1H2BC,HIST1H2BD,HIST1H2BE,HIST1H2BF,HIS T1H2BH,HIST1H2BI,HIST1H2BJ,HIST1H2BL,HIST1H2BN,HIST1H 2BO,HIST1H4F,HIST1H4H,HIST1H4J,HIST1H4K,HLA-DQB1,HLA- DRB4
658418Viral carcinogenesis1017CCNE1,HIST1H2BB,HIST1H2BC,HIST1H2BD,HIST1H2BE,HIST1H2 BF,HIST1H2BH,HIST1H2BI,HIST1H2BJ,HIST1H2BL,HIST1H2BN, HIST1H2BO,HIST1H4F,HIST1H4H,HIST1H4J,HIST1H4K,PMAIP1
585563Alcoholism1016GRIN2C,HIST1H2BB,HIST1H2BC,HIST1H2BD,HIST1H2BE,HIST1H 2BF,HIST1H2BH,HIST1H2BI,HIST1H2BJ,HIST1H2BL,HIST1H2BN, HIST1H2BO,HIST1H4F,HIST1H4H,HIST1H4J,HIST1H4K
83055p53 signaling pathway1010BBC3,CCNB1,CCNB2,CCNE1,CCNG2,DDB2,GADD45A,IGFBP3,PM AIP1,RRM2
83045Mismatch repair5.39071896706EXO1,LIG1,MSH2,POLD1,RFC4,RFC5
83039DNA replication5.28092675707LIG1,MCM2,MCM3,MCM6,POLD1,RFC4,RFC5
83054Cell cycle4.50185194711BUB1,CCNB1,CCNB2,CCNE1,GADD45A,MAD2L1,MCM2,MCM3,M CM6,PTTG1,TTK
413353Methionine degradation2.96176519203DNMT1,DNMT3B,MAT1A
413350Serine biosynthesis, glycerate-3P=> serine2.94579454902PHGDH,PSAT1
172847Protein digestion and absorption2.71826455107COL14A1,COL1A1,COL27A1,COL3A1,COL4A5,COL5A2,DPP4
1404797Platinum drug resistance1.84923509505BBC3,BIRC5,MSH2,PMAIP1,TOP2A
Pathway interaction database
137935FOXM1 transcription factor network5.19710032907BIRC5,CCNB1,CCNB2,CENPF,NEK2,TGFA,XRCC1
137934E2F transcription factor network4.06073289808CCNE1,MCM3,MYBL2,RRM2,SULT2A1,TK1,TYMS,XRCC1
137959BARD1 signaling events3.64916739205BARD1,CCNE1,FANCA,FANCG,RAD51
137939Direct p53 effectors3.5720579410BBC3,CCNB1,DDB2,GADD45A,IGFBP3,MSH2,PMAIP1,PPP1R13B,T GFA,TP53INP1
Table 3 (continued) BIOCYC
Pathway IDPathway nameLogPGene countGenes
169351Validated targets of C-MYC transcriptional activation2.29399887406BIRC5,CCNB1,CDCA7,MMP9,PMAIP1,TK1
137972Signaling events mediated by HDAC Class III2.16033401404HIST1H4F,HIST 1H4H,HIST1H4J,HIST1H4K
138080Aurora B signaling2.16033401404BIRC5,BUB1,CDCA8,RACGAP1
138054Nectin adhesion pathway1.90523529103CDH1,CLDN1,F11R
138064Syndecan-4-mediated signaling events1.65144786203FN1,LAMA3,MMP9
137925Aurora A signaling1.65144786203BIRC5,GADD45A,TPX2
138062Signaling events mediated by HDAC Class II1.54570597903ANKRA2,NCOR2,NR3C1
REACTOME 1269738SIRT1 negatively regulates rRNA Expression1016HIST1H2BB,HIST1H2BC,HIST1H2BD,HIST1H2BE,HIST1H2BF,HIST 1H2BH,HIST1H2BI,HIST1H2BJ,HIST1H2BL,HIST1H2BN,HIST1H2 BO,HIST1H4F,HIST1H4H,HIST1H4J,HIST1H4K,TAF1C
1269734Epigenetic regulation of gene expression1020DNMT1,DNMT3B,EZH2,HIST1H2BB,HIST1H2BC,HIST1H2BD ,HIST1H2BE,HIST1H2BF,HIST1H2BH,HIST1H2BI,HIST1H2B J,HIST1H2BL,HIST1H2BN,HIST1H2BO,HIST1H4F,HIST1H4H ,HIST1H4J,HIST1H4K,TAF1C,UHRF1
1269855Deposition of new CENPA-containing nucleosomes at the centromere1016HIST1H2BB,HIST1H2BC,HIST1H2BD,HIST1H2BE,HIST1H2BF,HIST 1H2BH,HIST1H2BI,HIST1H2BJ,HIST1H2BL,HIST1H2BN,HIST1H2 BO,HIST1H4F,HIST1H4H,HIST1H4J,HIST1H4K,OIP5
1269856Telomere maintenance1019HIST1H2BB,HIST1H2BC,HIST1H2BD,HIST1H2BE,HIST1H2B F,HIST1H2BH,HIST1H2BI,HIST1H2BJ,HIST1H2BL,HIST1H2 BN,HIST1H2BO,HIST1H4F,HIST1H4H,HIST1H4J,HIST1H4K ,LIG1,POLD1,RFC4,RFC5
1339139Activation of HOX genes during differentiation1017EZH2,HIST1H2BB,HIST1H2BC,HIST1H2BD,HIST1H2BE,HIST1H2B F,HIST1H2BH,HIST1H2BI,HIST1H2BJ,HIST1H2BL,HIST1H2BN,HI ST1H2BO,HIST1H4F,HIST1H4H,HIST1H4J,HIST1H4K,NCOA6
1269737Negative epigenetic regulation of rRNA expression1018DNMT1,DNMT3B,HIST1H2BB,HIST1H2BC,HIST1H2BD,HIST1H 2BE,HIST1H2BF,HIST1H2BH,HIST1H2BI,HIST1H2BJ,HIST1H 2BL,HIST1H2BN,HIST1H2BO,HIST1H4F,HIST1H4H,HIST1H4- J,HIST1H4K,TAF1C
1269864Packaging of telomere ends1015HIST1H2BB,HIST1H2BC,HIST1H2BD,HIST1H2BE,HIST1H2BF,HIST 1H2BH,HIST1H2BI,HIST1H2BJ,HIST1H2BL,HIST1H2BN,HIST1H2 BO,HIST1H4F,HIST1H4H,HIST1H4J,HIST1H4K
1269723Transcriptional regulation by small RNAs1016HIST1H2BB,HIST1H2BC,HIST1H2BD,HIST1H2BE,HIST1H2BF,HIST 1H2BH,HIST1H2BI,HIST1H2BJ,HIST1H2BL,HIST1H2BN,HIST1H2 BO,HIST1H4F,HIST1H4H,HIST1H4J,HIST1H4K,NUP107
1269659RNA polymerase I promoter opening1015HIST1H2BB,HIST1H2BC,HIST1H2BD,HIST1H2BE,HIST1H2BF,HIST 1H2BH,HIST1H2BI,HIST1H2BJ,HIST1H2BL,HIST1H2BN,HIST1H2 BO,HIST1H4F,HIST 1H4H,HIST1H4J,HIST1H4K

Table 3 (continued)

BIOCYC

Pathway IDPathway nameLogPGene countGenes
1269741Cell cycle1054BARD1,BIRC5,BUB1,CCNB1,CCNB2,CCNE1,CDCA5,CDCA8,CDT1 ,CENPF,CEP192,EXO1,GMNN,HIST1H2BB,HIST1H2BC,HIST1H2 BD,HIST1H2BE,HIST1H2BF,HIST1H2BH,HIST1H2BI,HIST1H2BJ, HIST1H2BL,HIST1H2BN,HIST1H2BO,HIST1H4F,HIST1H4H,HIST 1H4J,HIST1H4K,HMMR,KIF18A,KNTC1,LIG1,MAD2L1,MCM2,M CM3,MCM6,MCM8,MYBL2,NEK2,NUP107,OIP5,POLD1,PTTG1,R AD51,RFC4,RFC5,RRM2,SPC25,STAG3,TMPO,TOP2A,TPX2,TYM S,ZWINT
1269650Generic transcription pathway4.72069556136BARD1,BBC3,BIRC5,CCNB1,CCNE1,DDB2,DYRK2,EXO1,GADD45 A,IGFBP3,KIT,MAPKAPK5,MSH2,MYBL2,NCOA6,NCOR2,NOTC H2,NR0B1,NR3C1,PLAGL1,PLK2,PMAIP1,PPP1R13B,PPP1R13L,R FC4,RFC5,SMYD2,TGFA,TP53INP1,TPX2,ZNF133,ZNF266,ZNF302 ,ZNF443,ZNF606,ZNF700
GenMAPP
MAP00271Methionine metabolism2.00400689802DNMT1,MAT1A
MAP00240Pyrimidine metabolism1.9756982104POLD1,RRM2,TK1,TYMS
MAP00790Folate biosynthesis1.6540098102GGH,TYMS
MSigDB C2 BIOCARTA
M6682CDK regulation of DNA replication4.71444233905CCNE1,CDT1,MCM2,MCM3,MCM6
M5884Ensemble of genes encoding core extracellular matrix including ECM glycoproteins, collagens and proteoglycans3.98181378816COL14A1,COL1A1,COL27A1,COL3A1,COL4A5,COL5A2,ESM1,FGG ,FN1,IGFBP3,LAMA3,LAMB1,MATN3,NTN4,POSTN,SPARC
M3005Genes encoding collagen proteins3.6956103106COL14A1,COL1A1,COL27A1,COL3A1,COL4A5,COL5A2
M5889Ensemble of genes encoding extracellular matrix and extracellular matrix-associated proteins2.48396702233ANGPT2,ANGPTL2,ANXA4,CCL19,COL14A1,COL1A1,COL27A 1,COL3A1,COL4A5,COL5A2,CXCL9,ESM1,FGG,FN1,IGFBP3,L AMA3,LAMB1,LGALS2,LGALS3,LTB,MATN3,MMP28,MMP9, MUC20,NTN4,PLXDC1,POSTN,SERPINA3,SLPI,SPARC,SULF2,TG FA,WNT5A
M16966Stathmin and breast cancer resistance to antimicrotubule agents2.24319639803CCNB1,CD2,CD3D
M5887Genes encoding structural components of basement membranes2.12117892704COL4A5,LAMA3,LAMB1,NTN4
M3008Genes encoding structural ECM glycoproteins1.81844460809FGG,FN1,IGFBP3,LAMA3,LAMB1,MATN3,NTN4,POSTN,SPARC
M7239Apoptotic DNA fragmentation and tissue homeostasis1.80916522902HMGB2,TOP2A
M3075Granzyme A mediated apoptosis pathway1.72760766902GZMA,HMGB2
M12012p38 MAPK pathway03GADD45A,HSPB1,MAPKAPK5
PantherDB
P00034Integrin signaling pathway2.77657183110COL14A1,COL1A1,COL27A1,COL3A1,COL4A5,COL5A2,FN1,LAM A3,LAMB1,NTN4
P02776Serine glycine biosynthesis2.4342771402PHGDH,PSAT1
P00059p53 pathway2.3472680706CCNB1,CCNE1,DDB2,GADD45A,IGFBP3,RRM2
Table 3 (continued) BIOCYC
Pathway IDPathway nameLogPGene countGenes
P00004Alzheimer disease-presenilin pathway1.62540306606CDH1,FZD6,MMP28,MMP9,NOTCH2,WNT5A
P02739De novo pyrimidine deoxyribonucleotide biosynthesis1.5256513402RRM2,TYMS
P00045Notch signaling pathway1.45073760603JAG1,NCOR2,NOTCH2
P00017DNA replication1.41661325302POLD1,TOP2A
P02759Pyridoxal-5-phosphate biosynthesis1.41092242701PSAT1
P00050Plasminogen activating cascade1.36779245402FGG,MMP9
Pathway ontology
PW:0000662Mismatch repair pathway5.05407389106EXO1,LIG1,MSH2,POLD1,RFC4,RFC5
PW:0000130Nucleotide excision repair3.40861222502LIG1,POLD1
PW:0000088G1/S transition2.94579454902CCNB1,CCNE1
PW:0000129Base excision repair2.65047789502LIG1,XRCC1
PW:0000104Intrinsic apoptotic2.6335212404BBC3,BMF,HRK,PMAIP1
PW:0000349Alagille syndrome1.69904773601JAG1
PW:0000157Glycosaminoglycan metabolic1.69904773601GUSB
PW:0000095G1/S DNA-damage checkpoint1.69904773601CCNE1
PW:0000189Folate mediated one-carbon metabolic1.46905898202GGH,TYMS
PW:0000091G2/M transition1.41092242701CCNB1
PW:0000299Myocardial infarction1.41092242701LGALS2
SMPDB
SMP00144Adenosine deaminase deficiency1.69904773601ADA
Table 4 The enriched GO terms of the upregulated differentially-expressed genes
GO IDCATEGORYGO nameLogPGene countGenes
GO:0048514BPBlood vessel morphogenesis1038ADAMTS1,ADM,ANGPTL4,APOE,CCL 13,CCL2,CCN3,CDH2,CITED1,CXCL1 2,DCN,DLL1,ENPP2,FGF9,FZD4,GAT A6,GJA1,HAND2,HES1,HOXA5,HOX A7,IL6,JUNB,NR4A1,NRXN3,PDGFR A,RAMP1,SCG2,SIRT1,SRPX2,STARD 13,STAT1,TFAP2B,TGFBR3,THBS1,TI PARP,UNC5B,XBP1
GO:0051707BPResponse to other organism1044ABR,ADM,CASP9,CCL13,CCL2,CEBP B,CHGA,CITED1,CXCL1,CXCL12,C XCL2,CYP17A1,DCN,DNAJC3,EDN RB,FCN2,FGF7,HP,ICAM1,IER3,IL6,J UNB,KCNQ1,LITAF,MGST1,MTSS1, NPY,P2RY2,PDK4,PENK,PLA2G4A,P TGIR,PTX3,S100A8,S100A9,SCARB1, SLC25A19,SOCS3,SPON2,STAT1,TH, TIMP4,TNFRSF11B,XBP1
GO:0043069BPNegative regulation of programmed cell death1039ANGPTL4,APOE,CCL2,CD38,CEBPB,C ITED1,CRLF1,CTH,CXCL12,DHCR24 ,DLL1,DNAJC3,EDNRB,GATA6,GCL M,GRK5,HAND2,HSPA1A,HSPA5,IC AM1,IER3,IL6,NR4A1,NR4A2,NR4A3 ,PDK4,RGN,SCG2,SIRT1,SNAI1,SOCS 3,STAT3,TBX3,TFAP2B,TGFBR3,THB S1,UNC5B,XBP1,YWHAZ
GO:0001944BPVasculature development1042ADAMTS1,ADM,ANGPTL4,APOE,CC L13,CCL2,CCN3,CDH2,CITED1,CTH, CXCL12,DCN,DLL1,EGR1,ENPP2,FG F9,FZD4,GATA6,GJA1,HAND2,HES1 ,HOXA5,HOXA7,IL6,JUNB,NR4A1,N RXN3,PDGFRA,RAMP1,SCG2,SIRT1, SOCS3,SRPX2,STARD13,STAT1,TBX 3,TFAP2B,TGFBR3,THBS1,TIPARP,U NC5B,XBP1
GO:0008207BPC21-steroid hormone metabolic process1008ADM,AKR1B1,CYP11A1,CYP11B2,CY P17A1,CYP21A2,DKK3,FDX1
GO:0035150BPRegulation of tube size1015ADM,ADRA2C,APOE,CD38,CHGA,DB H,EDNRB,GCLM,GJA1,HBB,ICAM1, NPY1R,P2RY2,SIRT1,TGFBR3
GO:0040012BPRegulation of locomotion1041ABR,ACVR1C,AOC3,APOE,ARHGAP1 8,CCL13,CCL2,CCN3,CXCL1,CXCL1 2,CXCL2,DCN,EFEMP1,EGR1,ENPP 2,FBLN1,FGF7,GTPBP4,HOXA7,HSP A5,ICAM1,IGFBP5,IL6,INSM1,IRS1, P2RY2,PDGFRA,PTP4A1,PTX3,RARR ES2,RGN,SCARB1,SCG2,SEMA3B,SE MA6A,SNAI1,SRPX2,STARD13,STAT 3,TGFBR3,THBS1
GO:0050880BPRegulation of blood vessel size1015ADM,ADRA2C,APOE,CD38,CHGA,DB H,EDNRB,GCLM,GJA1,HBB,ICAM1, NPY1R,P2RY2,SIRT1,TGFBR3
GO:0040013BPNegative regulation of locomotion1019ABR,ACVR1C,APOE,CCL2,CCN3,CXC L12,DCN,FBLN1,GTPBP4,HOXA7,IGF BP5,PTX3,RGN,SEMA3B,SEMA6A,ST ARD13,STAT3,TGFBR3,THBS1
Table 4 (continued)
GO IDCATEGORYGO nameLogPGene count Genes
GO:0033993BPResponse to lipid1056ABR,ADAMTS1,ADH1C,ADM,CASP9,C CL13,CCL2,CD38,CEBPB,CITED1,CR H,CXCL1,CXCL2,CYP17A1,CYP26B1, DCN,EDNRB,FGF23,FOSL2,FZD4,GA TA6,ICAM1,IGFBP2,IL6,JUNB,LDLR- ,LITAF,MGST1,NEFH,NPC1,NPY1R,N R2F1,NR4A1,NR4A2,NR4A3,P2RY2,P DK4,PENK,PID1,PLA2G4A,PON1,PT GIR,S100A8,SCARB1,SIRT1,SOCS3,S PON2,STAT1,STAT3,TGFBR3,TH,THB- S1,TIMP4,TNFRSF11B,WFDC1,XBP1
GO:0031012CCExtracellular matrix1024ADAMTS1,ADAMTS9,ANGPTL4,APO E,CCN3,CTSD,DCN,EFEMP1,FBLN1, FBLN5,FGF9,FMOD,IL1RL1,LUM,M FAP4,PLAT,RARRES2,SPOCK3,SPO N2,TGFBR3,THBS1,TIMP4,TNFRSF1 1B,TNXB
GO:0005615CCExtracellular space1068ADAMTS9,ADM,AKR1B1,ANGPTL1,A NGPTL4,AOC3,APOC1,APOE,ATP4A ,C1S,CCL13,CCL2,CHGA,CPE,CRH,C RLF1,CTSD,CXCL1,CXCL12,CXCL2, DCN,DKK3,EFEMP1,ENPP2,FBLN1,F BLN5,FCN2,FGF12,FGF23,FGF7,FGF 9,FJX1,FMOD,GDF15,HBB,HP,HSPA 1A,ICAM1,IGFBP2,IGFBP5,IGFBP6,I L1RL1,IL6,LDLR,LUM,NPY,PI16,PLA T,PON1,PTX3,RAMP1,S100A8,S100A 9,SAA1,SCG2,SEMA3B,SERPING1,SP OCK3,SPON2,SRPX2,TGFBR3,THBS1 ,TIMP4,TNFRSF11B,TNXB,VASN,WF DC1,YWHAZ
GO:0031410CCCytoplasmic vesicle1049ADAMTS1,APOE,ATP1B3,CCL13,CCL 2,CD163,CHGA,CHGB,CPE,CTSD,CY B561,DBH,DDC,DLL1,DUSP16,ECE2 ,FZD4,GABARAPL1,GJA1,HBB,HP,H SPA5,IGFBP2,KCNQ1,LDLR,MARCO ,MTSS1,NPTX1,NPY1R,PLA2G4A,PL AT,RAB20,RAB21,RAB34,RAB38,RA RRES2,SAA1,SCAP,SCARB1,SCG2,SC G3,SERPING1,SLC18A1,SLC2A3,SYT 13,SYT4,TH,THBS1,YWHAZ
GO:0044433CCCytoplasmic vesicle part1029APOE,CD163,CHGA,CPE,DBH,ECE2,F ZD4,GABARAPL1,GJA1,HBB,HP,KC NQ1,LDLR,MARCO,RAB20,RAB21,R AB34,RAB38,RARRES2,SAA1,SCAP, SCARB1,SCG3,SERPING1,SLC18A1, SLC2A3,SYT4,TH,THBS1,YWHAZ
GO:0097708CCIntracellular vesicle1048ADAMTS1,APOE,ATP1B3,CCL13,CCL 2,CD163,CHGA,CHGB,CPE,CTSD,CY B561,DBH,DDC,DLL1,DUSP16,ECE2 ,FZD4,GABARAPL1,GJA1,HBB,HP,H SPA5,IGFBP2,KCNQ1,LDLR,MARCO ,MTSS1,NPTX1,NPY1R,PLA2G4A,PL AT,RAB20,RAB21,RAB34,RAB38,RA RRES2,SAA1,SCAP,SCARB1,SCG2,SC G3,SERPING1,SLC18A1,SLC2A3,SYT 13,SYT4,TH,THBS1,YWHAZ
GO:0071953CCElastic fiber4.72830068103FBLN1,FBLN5,MFAP4
Table 4 (continued)
GO IDCATEGORYGO nameLogPGene countGenes
GO:0030659CCCytoplasmic vesicle membrane4.66565563723CD163,CHGA,CPE,DBH,ECE2,FZD4,G ABARAPL1,GJA1,KCNQ1,LDLR,MAR CO,RAB20,RAB21,RAB34,RAB38,SC AP,SCARB1,SCG3,SLC18A1,SLC2A3, SYT4,TH,YWHAZ
GO:0098857CCMembrane microdomain4.64446419518ATP1B3,CDH2,CPE,CTSD,DLL1,EDNR B,GJA1,GPM6B,ICAM1,IRS1,KCNQ1, LDLR,NPC1,PRKAR1A,PRKAR2B,SC ARB1,SLC2A3,UNC5B
GO:0045121CCMembrane raft4.64446419518ATP1B3,CDH2,CPE,CTSD,DLL1,EDNR B,GJA1,GPM6B,ICAM1,IRS1,KCNQ1, LDLR,NPC1,PRKAR1A,PRKAR2B,SC ARB1,SLC2A3,UNC5B
GO:0030424CCAxon4.44244685724ADRA2C,CCL13,CCL2,CCN3,CLDN5,C RH,CYP17A1,DBH,DDC,DLG2,GRIK 1,NEFH,NPY,NPY1R,PENK,PNMT,RA B21,SEMA6A,SIRT1,SLC1A2,STAT1,S TMN2,TH,UCHL1
GO:0008201MFHeparin binding1014ADAMTS1,APOE,CCL13,CCL2,CCN3,F GF12,FGF7,FGF9,FMOD,LXN,SAA1,T GFBR3,THBS1,TNXB
GO:0001664MFG protein-coupled receptor binding1020ADM,ADRA2C,CCL13,CCL2,CRH,CXC L1,CXCL12,CXCL2,EDNRB,GNAZ,HS PA1A,MRAP,NPY,P2RY2,PENK,RAM P1,SAA1,STAT1,STAT3,UCHL1
GO:0005539MFGlycosaminoglycan binding1016ADAMTS1,APOE,CCL13,CCL2,CCN3,D CN,FGF12,FGF7,FGF9,FMOD,LXN,SA A1,SPOCK3,TGFBR3,THBS1,TNXB
GO:0004497MFMonooxygenase activity1012CH25H,CYP11A1,CYP11B2,CYP17A1,C YP21A2,CYP26B1,CYP4B1,DBH,FDX 1,FMO2,FMO3,TH
GO:1901681MFSulfur compound binding5.69297495217ADAMTS1,APOE,CCL13,CCL2,CCN3, FGF12,FGF7,FGF9,FMOD,LXN,MGS T1,PC,SAA1,SOAT1,TGFBR3,THBS1 ,TNXB
GO:0000982MFTranscription factor activity, RNA poly- merase II proximal promoter sequence- specific DNA binding5.40691233120CEBPB,CEBPD,EGR1,FOSL2,FOXK2,H AND2,HES1,HOXA5,HOXA7,INSM1, JUNB,NFIL3,NR4A1,NR4A2,NR4A3,P HOX2B,SNAI1,STAT3,TBX3,TFAP2B
GO:0001047MFCore promoter binding5.3856147713CEBPB,CREM,EGR1,GATA6,INSM1,NF IL3,NR4A2,NR4A3,SFPQ,SIRT1,STAT 1,TFAP2B,XBP1
GO:0016491MFOxidoreductase activity4.99741777830AASS,ADH1A,ADH1B,ADH1C,AKR1B 1,ALDH1A1,ALDH1A3,ALDH3A2,AO C3,AOX1,CH25H,CYB561,CYP11A1,C YP11B2,CYP17A1,CYP21A2,CYP26B 1,CYP4B1,DBH,DHCR24,FDX1,FMO2 ,FMO3,GSTT2,HBB,HEPH,HSD3B1,H SD3B2,MGST1,TH
GO:0035259 GO:0031406MF MFGlucocorticoid receptor binding Carboxylic acid-binding4.909190407 4.85582049705 15CEBPB,NR4A1,NR4A2,NR4A3,STAT3
APOC1,CYP26B1,DBH,DDC,FMO3,GRI K1,MAT2A,PC,PCK1,S100A8,S100A9, SCARB1,SYT4,TH,THBS1
Table 5 The enriched GO terms of the down-regulated differentially-expressed genes
GO IDCATEGORYGO nameLogPGene countGenes
GO:0044770BPCell cycle phase transition1030ANLN,BIRC5,BUB1,CABLES1,CC NB1,CCNB2,CCNE1,CDCA5,CD KN3,CDT1,CENPF,CEP192,EZH2 ,GADD45A,HMMR,KNTC1,MAD 2L1,MCM2,MCM3,MCM6,MCM8, MELK,NEK2,PLAGL1,PLK2,RRM- 2,TIMELESS,TPX2,TTK,TYMS
GO:0051985BPNegative regulation of chromosome segregation1008BUB1,CCNB1,CENPF,CEP192,CHTF18, MAD2L1,PTTG1,TTK
GO:0006323BPDNA packaging1025CCNB1,CDCA5,CHAF1A,CHAF1B,H2 BFS,HIST1H1C,HIST1H2BB,HIST1H 2BC,HIST1H2BD,HIST1H2BE,HIST1 H2BF,HIST1H2BH,HIST1H2BI,HIST 1H2BJ,HIST1H2BL,HIST1H2BN,HIS T1H2BO,HIST1H4F,HIST1H4H,HIST 1H4J,HIST1H4K,HMGB2,MCM2,OIP 5,TOP2A
GO:0007088BPRegulation of mitotic nuclear division1015ANLN,BIRC5,BUB1,CCNB1,CDCA5,CE NPF,CEP192,HOXA13,KIF11,KNTC1, MAD2L1,NEK2,PTTG1,TGFA,TTK
GO:0034728BPNucleosome organization1022CHAF1A,CHAF1B,H2BFS,HIST1H1C, HIST1H2BB,HIST1H2BC,HIST1H2B D,HIST1H2BE,HIST1H2BF,HIST1H2 BH,HIST1H2BI,HIST1H2BJ,HIST1H 2BL,HIST1H2BN,HIST1H2BO,HIST1 H4F,HIST1H4H,HIST1H4J,HIST1H4K, HMGB2,MCM2,OIP5
GO:0072331BPSignal transduction by p53 class media- tor1018BARD1,BBC3,CCNB1,DYRK2,EXO1,G ADD45A,MAPKAPK5,MSH2,PLAGL1 ,PLK2,PMAIP1,PPP1R13B,PPP1R13L, RFC4,RFC5,SMYD2,TP53INP1,TPX2
GO:0007062BPSister chromatid cohesion Cell cycle process1013 71BIRC5,BUB1,CDCA5,CDCA8,CENPF,K IF18A,KIF22,KNTC1,MAD2L1,NUP10 7,SPC25,STAG3,ZWINT ANLN,ASPM,BARD1,BIRC5,BUB1,CA BLES1,CCNB1,CCNB2,CCNE1,CCNG 2,CDCA2,CDCA5,CDCA8,CDKN3,CD T1,CENPF,CEP192,CHTF18,CKAP2,E 2F8,EML1,EZH2,FANCA,FANCG,FA P,GADD45A,HMMR,HOXA13,KIF11, KIF18A,KIF22,KNTC1,LIG1,MAD2L1 ,MCM2,MCM3,MCM6,MCM8,MELK, MSH2,MYBL2,NEK2,NEK3,NOTCH2, NR3C1,NUP107,OIP5,PBK,PHGDH,PI MREG,PLAGL1,PLK2,PRC1,PTTG1,R AB11FIP4,RACGAP1,RAD51,RAD54L ,RRM2,SPAG5,SPC25,STAG3,TGFA,T IMELESS,TOP2A,TP53INP1,TPX2,TT K,TYMS,WNT5A,ZWINT
GO:0022402BP10
GO:0043062BPExtracellular structure organization1023CDH1,COL14A1,COL1A1,COL27A1,CO L3A1,COL4A5,COL5A2,DDR1,DPP4, F11R,FAP,FGG,FN1,LAMA3,LAMB1, LGALS3,MATN3,MMP9,POSTN,SPAR C,SULF2,TPSAB1,VCAM1
GO:0007051BPSpindle organization1015ASPM,BIRC5,CCNB1,CEP192,EML1,KI F11,MYBL2,NEK2,PLK2,PRC1,RACG AP1,SPAG5,SPC25,TPX2,TTK
Table 5 (continued)
GO IDCATEGORY GO nameLogPGene countGenes
GO:0000775CC Chromosome, centromeric region1019BIRC5,BUB1,CCNB1,CDCA5,CDCA8,C ENPF,DNMT1,DNMT3B,KIF18A,KIF2 2,KNTC1,MAD2L1,NEK2,NUP107,OI P5,SPAG5,SPC25,STAG3,ZWINT
GO:0005819CC Spindle1021ASPM,BIRC5,CCNB1,CDCA8,CENPF,C KAP2,EML1,HSPB1,KIF11,KIF18A,K IF22,KNTC1,MAD2L1,NEK2,NR3C1, PRC1,RAB11FIP4,RACGAP1,SPAG5, TPX2,TTK
GO:0005615CC Extracellular space1056ADA,AMY1A,AMY2A,AMY2B,ANGP T2,ANGPTL2,CCL19,COL14A1,COL1 A1,COL3A1,CPM,CXCL9,DDR1,FAB P3,FAP,FGG,FN1,GGH,GUSB,H2BFS, HIST1H2BC,HIST1H2BE,HIST1H2BF ,HIST1H2BI,HIST1H2BJ,HMGB2,HSP B1,IGFBP3,IGHM,IGLL1,KIT,LAMB1 ,LCN2,LGALS3,LRIG3,LTB,MICA,M MP9,NUDT1,PLA2G1B,PLXDC1,PNL IPRP2,POSTN,PRSS8,RAB11FIP4,SE MG1,SERPINA3,SLPI,SPARC,STAG3 ,SULF2,TGFA,TPSAB1,VCAM1,WNT 5A,ZG16B
GO:0000785CC Chromatin1038BRD8,CDCA5,CENPF,CHAF1A,CHAF 1B,DNMT1,DNMT3B,ENC1,EZH2,H2 BFS,HIST1H1C,HIST1H2BB,HIST1H2 BC,HIST1H2BD,HIST1H2BE,HIST1H 2BF,HIST1H2BH,HIST1H2BI,HIST1H 2BJ,HIST1H2BL,HIST1H2BN,HIST1H 2BO,HIST1H4F,HIST1H4H,HIST1H4J ,HIST1H4K,HMGB2,IGFBP3,KIF22,M CM2,NCOR2,OGT,OIP5,PLK2,RAD51, TIMELESS,TMPO,UHRF1
GO:0044427CC Chromosomal part1061BIRC5,BRD8,BUB1,CCNB1,CDCA5,CD CA8,CENPF,CHAF1A,CHAF1B,CHTF 18,DNMT1,DNMT3B,ENC1,EZH2,H2 BFS,HIST1H1C,HIST1H2BB,HIST1H2 BC,HIST1H2BD,HIST1H2BE,HIST1H 2BF,HIST1H2BH,HIST1H2BI,HIST1H 2BJ,HIST1H2BL,HIST1H2BN,HIST1H 2BO,HIST1H4F,HIST1H4H,HIST1H4J ,HIST1H4K,HMBOX1,HMGB2,IGFBP 3,KIF18A,KIF22,KNTC1,MAD2L1,MC M2,MCM3,MCM6,MSH2,MYBL2,NC OR2,NEK2,NUP107,OGT,OIP5,PLK2, POLD1,RAD51,RFC4,RFC5,SPAG5,SP C25,STAG3,THOC3,TIMELESS,TMPO ,UHRF1,ZWINT
GO:0000788CC Nuclear nucleosome1012H2BFS,HIST1H2BB,HIST1H2BC,HIST1 H2BD,HIST1H2BE,HIST1H2BF,HIST1 H2BH,HIST1H2BI,HIST1H2BJ,HIST1 H2BL,HIST1H2BN,HIST1H2BO
Table 5 (continued)
GO IDCATEGORYGO nameLogPGenecount Genes
GO:0000228CCNuclear chromosome1043BIRC5,BRD8,BUB1,CCNB1,CDCA5,CH AF1A,CHAF1B,DNMT3B,ENC1,EZH 2,H2BFS,HIST1H1C,HIST1H2BB,HIS T1H2BC,HIST1H2BD,HIST1H2BE,HI ST1H2BF,HIST1H2BH,HIST1H2BI,H IST1H2BJ,HIST1H2BL,HIST1H2BN,H IST1H2BO,HIST1H4F,HIST1H4H,HIS T1H4J,HIST1H4K,HMBOX1,HMGB2,I GFBP3,MCM2,MCM3,MCM6,MSH2,N COR2,NEK2,POLD1,RAD51,STAG3,T HOC3,TIMELESS,TOP2A,UHRF1
GO:0032993CCProtein-DNA complex1020H2BFS,HHEX,HIST1H1C,HIST1H2BB, HIST1H2BC,HIST1H2BD,HIST1H2BE ,HIST1H2BF,HIST1H2BH,HIST1H2B I,HIST1H2BJ,HIST1H2BL,HIST1H2B N,HIST1H2BO,HIST1H4F,HIST1H4H,- HIST1H4J,HIST1H4K,MCM3,POLD1
GO:0044454CCNuclear chromosome part1040BRD8,BUB1,CCNB1,CDCA5,CHAF1A ,CHAF1B,DNMT3B,ENC1,EZH2,H2B FS,HIST1H1C,HIST1H2BB,HIST1H2 BC,HIST1H2BD,HIST1H2BE,HIST1H 2BF,HIST1H2BH,HIST1H2BI,HIST1H 2BJ,HIST1H2BL,HIST1H2BN,HIST1H 2BO,HIST1H4F,HIST1H4H,HIST1H4J, HIST1H4K,HMBOX1,HMGB2,IGFBP3 ,MCM2,MCM3,MCM6,MSH2,NCOR2 ,POLD1,RAD51,STAG3,THOC3,TIME LESS,UHRF1
GO:0000790CCNuclear chromatin1025BRD8,CDCA5,CHAF1A,CHAF1B,DNM T3B,ENC1,EZH2,H2BFS,HIST1H1C,H IST1H2BB,HIST1H2BC,HIST1H2BD ,HIST1H2BE,HIST1H2BF,HIST1H2B H,HIST1H2BI,HIST1H2BJ,HIST1H2B L,HIST1H2BN,HIST1H2BO,HMGB2,I GFBP3,NCOR2,TIMELESS,UHRF1
GO:0046983MFProtein dimerization activity1047AHR,ASNS,BARD1,BIRC5,BTBD11,C D2,CD3D,CENPF,DPP4,E2F8,FAP,GZ MA,H2BFS,HHEX,HIST1H2BB,HIST 1H2BC,HIST1H2BD,HIST1H2BE,HI ST1H2BF,HIST1H2BH,HIST1H2BI,H IST1H2BJ,HIST1H2BL,HIST1H2BN,H IST1H2BO,HIST1H4F,HIST1H4H,HIS T1H4J,HIST1H4K,HLA-DQB1,HOME R1,HPGD,KIT,LCN2,MAD2L1,MAT1 A,MSH2,NCOA6,NR0B1,NR3C1,RAB 11FIP4,SRGAP2,TCFL5,TIMELESS,T OP2A,TYMS,UGT1A6
GO:0046982MFProtein heterodimerization activity5.93827075427AHR,BARD1,BIRC5,BTBD11,CD3D,H 2BFS,HIST1H2BB,HIST1H2BC,HIST 1H2BD,HIST1H2BE,HIST1H2BF,HIS T1H2BH,HIST1H2BI,HIST1H2BJ,HIS T1H2BL,HIST1H2BN,HIST1H2BO,H IST1H4F,HIST1H4H,HIST1H4J,HIST1 H4K,HLA-DQB1,HOMER1,NR3C1,TI MELESS,TOP2A,UGT1A6
GO:0004556MFAlpha-amylase activity4.3536450903AMY1A,AMY2A,AMY2B
GO:0005201MFExtracellular matrix structural constitu- ent4.34385718108COL14A1,COL1A1,COL27A1,COL3A1, COL4A5,COL5A2,LAMB1,MATN3
GO:0000217MFDNA secondary structure binding4.30511444405HMGB2,HMGB3,MSH2,NR0B1,RAD51
Table 5 (continued)
GO IDCATEGORYGO nameLogPGene countGenes
GO:0043142MFSingle-stranded DNA-dependent ATPase activity4.18338438904CHTF18,RAD51,RFC4,RFC5
GO:0000400MFFour-way junction DNA binding3.93515657704HMGB2,HMGB3,MSH2,RAD51
GO:0042802MFIdentical protein binding3.82710543241ANXA4,ASNS,BARD1,BIRC5,CD2,CEN PF,CHAF1A,CLDN1,COL1A1,DPP4,E 2F8,FAP,FHOD1,FN1,GZMA,HHEX,H OMER1,HPGD,HSPB1,IER5,KIT,LCN 2,MAD2L1,MAT1A,MCM6,MMP9,M SH2,NCOA6,NR0B1,NR3C1,PPP1R13 L,PRC1,RAB11FIP4,RAD51,SRGAP2, TIMELESS,TK1,TOP2A,TYMS,UGT1 A6,UHRF1
GO:0008301MFDNA binding, bending3.53271649804HHEX,HMGB2,HMGB3,TOP2A
GO:0033170MFProtein-DNA loading ATPase activity3.4508768103CHTF18,RFC4,RFC5
Fig. 5 Protein-protein inter- action (PPI) networks for differentially-expressed genes (DEGs). (Green round shape node represents upregulated genes). Green dots are also genes which are not hub or dif- ferential expressed genes

(degree = 100). Module 8 had 36 nodes and 74 edges. Hub genes in this modules such as UBD (degree=664), MAGED2 (degree=37), HIST1H1C (degree =144), MAD2L1 (degree=60), and PHGDH (degree=76). Module 10 had 29 nodes and 89 edges. Hub genes in this modules such as HSPB1 (degree=129), HIST1H2BJ (degree=23), VCAM1 (degree =671), UHRF1 (degree =35), MCM3 (degree =126), NCOR2 (degree = 140), HIST1H1C (degree =144), TOP2A (degree=110), FN1 (degree =1012), PBK (degree=91), ASNS (degree=43), MCM2 (degree = 110), TMPO (degree=58), MCM6 (degree = 100), HMGB2 (degree=39), HIST1H2BL (degree=21), TYMS (degree=39), CHAF1B (degree=26),

and PHGDH (degree =76). Module 27 had 17 nodes and 47 edges. Hub genes in this modules such as CCNE1 (degree =84), POLD1 (degree=67), CDT1 (degree=55), and PRC1 (degree =27).

Construction of target genes-miRNA regulatory network

Target genes (up and down regulated) interacts with miRNA are shown Figs. 12 and 13. Top five up regulated targeted genes such as YWHAZ interacts with 212 miRNAs, GATA6 interacts with 207 miRNAs, LDLR interacts with 167 miR- NAs, BZW1 interacts with 149 miRNAs, and IGFBP5

Table 6 Topology table for up and down regulated genes
RegulationNodeDegreeBetweennessStressClosenessClustering coefficient
UpYWHAZ8050.2601891.11E+080.4021170.001715
UpHSPA53940.102115430351160.3822520.004056
UpSTAT32130.051796226781720.3522060.006511
UpAPOE1830.031537147729640.3367130.029905
UpGRK51750.038557108968840.3535720.006043
UpSTAT11740.037604187476720.343990.005182
UpICAM11690.030647275298140.3227550
UpHP1600.014866109834320.3173420.038836
UpAPOC11510.01185758333580.3056570.044531
UpSH3BP51420.01498190894060.3324270.049146
UpTH1420.051469120722400.3296529.25E-04
UpSERPING11370.00991555512860.3119910.053456
UpNR4A11160.02882665141600.3614480.008096
UpMAP3K51130.02289783018640.3550240.011852
UpCD831110.0439651608500.3230670
UpSF11030.018338110668540.3230053.81E-04
UpPRKAR1A1020.02177389722040.3304550.002136
UpNOLC1990.01394146811020.3531230.021439
UpIRS1990.02033354129700.3571990.010513
UpHOXB2900.028436230270920.2558160
UpNDRG1890.01165448851780.3331340.00715
UpUCHL1840.01476453967900.3513670.016064
UpCEBPB830.01317268938760.335160.013811
UpCDH2770.02070548046980.3248670.002051
UpCXCL2750.024541153626660.2704570
UpPCK1720.01103362950120.323860
UpTHBS1720.02306560232940.3280770.004695
UpFUBP1700.01447464694840.3236720
UpS100A8610.01275848747000.3252680.009836
UpGPRASP1540.01461326983520.3188966.99E-04
UpJUNB540.01104643827180.3193020.003771
UpCASP9530.01000133940280.3172610
UpIPO7470.00654317866140.3408330.018501
UpDLG2460.01217720379800.2668440.006763
UpID2460.00991115963520.3336660.007729
UpCHGB430.00981413505120.2940420.002215
UpHES1430.00933221413740.3393570.022148
UpNEDD9420.00701119879300.3172410.004646
UpCCL2410.01150477091120.2585070
UpFBLN1410.00990522384540.2989680.003659
UpHSPA4L400.00548717826840.3231710.008974
UpCYP11A1380.00555910648060.2995040.048364
UpIL8380.01066318509700.2901620
UpCTSD370.00716127981380.3200560
UpPDGFRA370.00650713656520.3285930.024024
UpPLAT340.00581536539300.2864820.008065
UpMAT2A340.00667720893460.3216160.005348
UpSNAI1340.00551717008220.3170810.005348
UpIFI27330.0109617731500.3173020
UpNEFH320.0012497480580.316540
UpVASN310.00353514247100.3130620
Table 6 (continued)
RegulationNodeDegreeBetweennessStressClosenessClustering coefficient
UpDCN300.00661915983040.2961080.013793
UpNR4A2300.0046869496740.3010870.009195
UpATP5L300.0088318695020.314160
UpSTMN2290.00680313050760.3180660.002463
UpCALD1290.00411113140680.322030.009852
UpGJA1290.00486712218000.3164410
UpAKR1B1280.00673912011480.3125550
UpEGR1280.0033199010460.2992180.02381
UpNR2F1280.00553913488160.3214510.005291
UpCEBPD280.00347117404980.3214930.031746
UpPC270.0025817346600.316540.013333
UpGTPBP4260.00193312549460.3207730
UpPEG10260.00537912196720.3125350
UpHBB260.0045379430000.3241320.027692
UpTAGLN250.0048128374540.3240480.023333
UpPLA2G4A240.00317110865620.316720
UpRALYL230.00477110043280.3124380
UpERN1220.0045998121020.3315260.047619
UpPHF10220.00352611930740.314160
UpLDLR220.0047877887380.3339550.030303
UpGNAZ210.0040548980380.3145940
UpPRKAR2B200.0029427081560.3154450.005263
UpNPY200.00568621117220.2326680
UpNPTX1200.0047648002200.3130030
UpFRMD5200.0030258250160.3186730.010526
UpCPE200.0032756941460.3122820
UpBZW1190.0034678351640.3122630
UpDNAJB9180.0029164423020.3276050.026144
UpMAPK4180.0030717066580.3123010
UpGEM170.00414226479960.2551780
UpNOV170.0023353819240.2865470.029412
UpGCLM170.003667279900.3121850
UpABCB1160.0023815882360.3148310
UpDLL1160.0042284631660.3128470.010989
UpALAS1160.0020425448640.3134340
UpELL2160.0030985505000.3117190
UpCNN1160.0026865596860.3116610
UpFZD4160.006211516520.3163210.016667
UpHAND2150.0026199005780.3204450
UpCYP4B1150.00557721533260.2241190
UpTFAP2B150.00516479300.316860
UpSTARD13150.0023813533500.286040.009524
UpSAA1150.00557725360860.2084130
UpALDH3A2150.0021736324860.3122040
UpPTGIR150.0029035903140.3124770
UpNBEA150.0024384833440.3124180.009524
UpPRKD3150.002095199660.3117770
UpSERP1150.00293925651100.2681570
UpMRAS150.0024023878420.3119130
UpHOXA5140.002335773180.3133750
UpTGFBR3140.00317820409900.2578160
Table 6 (continued)
RegulationNodeDegreeBetweennessStressClosenessClustering coefficient
UpCXCL12140.00227314056520.2631050
UpCYP11B2140.0047818166600.2311030.010989
UpIER3140.0023687267580.3181470
UpNPC1130.0032373920860.3112160
UpLITAF130.0014834164060.3136690
UpLXN130.00320924830280.2413130
UpNFIL3130.002446117320.3156440
UpNAP1L5130.0022635900660.3128280
UpSCARB1138.76E-042406200.3185920.054545
UpSNAPC1130.0033882759260.3230670.025641
UpFGF7130.0014828278520.2434930
UpMCF2130.0030377813500.312710
UpMSI2132.53E-041691640.3122040
UpNGEF130.00250314631940.2438360
UpMTSS1130.0015062970380.3114090
UpPTP4A1130.0026815184200.3143380
UpEDNRB120.0021335351880.3145740
UpSCAP120.0017052921060.3114480
UpC1S120.0010683584180.2690780.111111
UpPAPSS2120.0014173828380.3135120
UpQPCT112.63E-042742860.3143180
UpCITED1119.91E-042956040.2835330
UpSDF2L1110.0011973248400.3151280
UpSYT4110.0021021630660.2518330
UpIGFBP2110.0012462996580.2323340.090909
UpCD38110.00281514322100.2423510
UpZNF331110.0014163017660.316860.018182
UpKCNK3100.0012073966620.2931990.133333
UpDHCR24100.0021985051540.3148510
UpFDX1100.0012742433380.2547890.071429
UpCCL13100.00172713283020.2529770
UpRAB38103.56E-042249440.3140230
UpSLC25A19100.0032173429040.3111390
UpDNAJC3106.45E-042461380.3120490
UpCXCL190.0020259232040.204220
UpLUM90.001258181920.2339270
UpFGF2390.0023959826300.2358530
UpCNN390.0019594359140.3146930.055556
UpTBX392.22E-041397900.2688040
UpCYP17A190.00240210389280.2463520
UpMRAP93.66E-04283060.2392520.285714
UpTLX290.0016537070660.2426790
UpP2RY294.77E-042161780.3141010
UpRAB3499.30E-042163240.3131010
UpABR98.46E-043390400.313610
UpGRIK190.0014532197260.3122630
UpINSM190.00141211797480.2492050
UpFOXK290.0013439573360.2586670
UpARFGAP380.0035074068660.3189770
UpPTX384.37E-041350440.2253990.107143
UpIL1RL180.00162211694100.2577890
Table 6 (continued)
RegulationNodeDegreeBetweennessStressClosenessClustering coefficient
UpSCG280.0014844726560.3156440
UpATP1B385.56E-042515080.3117190
UpSLC27A689.25E-042234480.312360
UpRPRM89.73E-046022300.2657130
UpANGPTL481.16E-04940940.2698750
UpADM86.45E-043126480.2210950
UpDUSP1682.75E-041997460.2575640
UpIL680.00159512787640.2119910
UpFOSL286.37E-044266080.3189160.107143
UpFGF1283.20E-042602340.2618820
UpALDH1A180.0013342465620.3118550
UpCTH80.0012591811340.3371890.035714
UpHSPA1A73.86E-044656320.3107920.190476
UpSEMA6A70.0014365680360.2565890
UpCLDN579.05E-041165140.3112550
UpADAMTS170.0013153281260.3139440
UpCGNL178.22E-05679720.3363520.285714
UpMT1A70.0013923371060.3114090
UpADH1B70.0015969343640.2457360
UpACVR1C79.66E-044214260.2482060
UpCHGA70.0014023256180.3147320
UpNR4A368.11E-046223400.2609420
UpSOAT169.01E-041397740.3112930
UpNRXN364.91E-04756320.2449680
UpFXC164.24E-042394120.2146590
UpCDH1860.0017122125580.3111580
UpSLC1A266.26E-0661460.2564570
UpDBH60.0015952880820.1930840
UpTMOD168.63E-046644960.24570
UpABTB263.90E-042516720.3143770
UpUNC5B60.0019941956500.3109840
UpCRH611210
UpSEMA3B60.0011968334960.1762760
UpPGM368.64E-042240620.3133360
UpMAP664.20E-04396340.2700340
UpMGST165.54E-04922440.3109070
UpGIPC254.09E-042588220.206720
UpCD16352.02E-04490980.2826380
UpMFAP458.65E-043624140.25510
UpTNXB54.17E-041707100.2247520
UpPID150.0015957167320.2044780
UpAOX155.59E-04437160.2568910
UpCRLF1512010
UpIL1R250.0015954632040.2068140
UpWFDC150.0012084627280.2301480
UpADRA2C50.0011964660680.2889410.1
UpFMOD51.55E-0582960.2044030
UpSLC2A359.84E-042652300.3124960
UpAASS52.52E-041448540.3144560
UpAOC340.0011962020140.2437890
UpDDC44.35E-043670460.237630
Table 6 (continued)
RegulationNodeDegreeBetweennessStressClosenessClustering coefficient
UpTIPARP44.32E-04702040.312010
UpFCN244.02E-042409440.2057360
UpFGF947.65E-0670000.2376750
UpPDK446.23E-04908660.3109070
UpDUSP545.68E-051018180.314910
UpADH1A42.29E-0616940.2293580
UpPON141.36E-05120940.240410
UpGPM6B44.72E-042226120.2696710
UpANGPTL143.99E-044165720.1471680
UpNPY1R48.50E-041209580.2103720
UpSRPX247.98E-044754480.2028890
UpDNER48.00E-043685260.2109650
UpGCKR44.32E-04594480.3114870
UpPLEK247.91E-05221000.3109070
UpPSD348.50E-04910620.3109070
UpKCNK534.30E-041123200.3127690
UpRAB203000.3107920
UpDNAJC1236.42E-05130300.2540920
UpTPMT34.08E-05788240.3129450
UpCHRNA337.98E-041657980.2057870
UpPDE8A32.85E-05382860.3114090
UpMT1G32.41E-04695280.3108690
UpENPP232.00E-05165100.2443470
UpTMEM2537.98E-045184540.2300840
UpST3GAL437.98E-04782660.3108690
UpC734.06E-041147720.2184460
UpRGN23.99E-041608920.2037550
UpARHGAP1821210
UpTNRC423.99E-041502220.2240290
UpAQP1122.26E-0621460.2458810
UpPENK21.45E-04306880.310830
UpFJX121210
UpTIMP422.09E-05256380.1992450
UpAGXT2L123.15E-05657520.312730
UpSLC33A128.92E-0674020.3108690
UpCYP26B124.25E-0635240.2595510
UpFMO321210
UpMT1F24.50E-05299540.310830
UpPNMT21.66E-064760.2171410
UpADH1C20000
UpMARCO21210
UpALDH1A321.95E-05394220.3119320
UpGSTA421.93E-05160300.3112350
UpSELK1000.2018920
UpADAMTS91000.2027090
UpDKK31000.2179620
UpBHMT21000.2449440
UpARHGAP361000.1393090
UpTCEAL71000.224270
UpNRXN31000.2316680
UpAS3MT1000.3107920
Table 6 (continued)
RegulationNodeDegreeBetweennessStressClosenessClustering coefficient
UpHEPH1000.2366210
UpSLC16A91000.3107920
UpAK71000.3107920
UpPHOX2B1000.3107920
UpMEDAG1000.2320970
UpHSD3B21000.2437170
UpG0S21000.1961740
UpMT1E1000.3107920
UpFNDC41000.2099490
DownFN110120.2471083.59E+080.4207350.001521
DownVCAM16710.1146712.23E+080.3925240.001188
DownUBD6640.1489222.86E+080.3757566.22E-04
DownBARD12520.051185434109480.349890.001644
DownTK11690.044886101925800.3788310.003593
DownHIST1H1C1440.01521395915040.3601580.018648
DownCDH11420.027298211407760.3414230.004295
DownNCOR21400.02482118622420.3511930.012436
DownBBC31370.00374738689820.3382480.040907
DownCABLES11350.00356639071980.3414450.041238
DownHSPB11290.02574281094680.3741830.006662
DownMCM31260.01836870529760.3909270.034667
DownCCNB11140.01120155064120.3501310.020183
DownTOP2A1100.01084154820280.3775110.030692
DownMCM21100.01351452857900.3755620.032193
DownKIT1010.02561594134260.331360
DownMCM61000.01205744742200.3806140.044242
DownRAD51920.01694974085760.3398730.008839
DownPBK910.00898775949900.3484060.006105
DownOGT880.01991980329480.3302430
DownCHAF1A860.00763969350840.3276290.012312
DownCCNE1840.009241495640.3472890.02008
DownCOL1A1840.02279931310700.364880.011761
DownFANCA780.01060362863220.3414910.01665
DownPHGDH760.01152746027520.3813840.015789
DownDDB2710.00859241000720.3352640.013682
DownDNMT3B670.00779831889160.3379340.019901
DownPOLD1670.00821638522400.3414910.019448
DownPSAT1630.00701436830600.345710.012801
DownSLPI600.021133465667180.2559040
DownMAD2L1600.01091425243920.3504920.014124
DownTMPO580.00678725172420.3489310.006655
DownCDT1550.00361418900660.3438890.052975
DownCHTF18530.00502833775160.3319650.019594
DownRFC5490.0022715561580.3306710.033163
DownHIST1H2BB490.00378619878420.33080.002551
DownXRCC1490.00659330013880.3322460.011905
DownDYRK2460.00491437700240.329580
DownZWINT450.00645522628640.3331590.055556
DownMYBL2440.00441516111820.3198920.014799
DownBUB1440.0046317594300.3374410.059197
DownNUP107430.00620320334460.3447970.015504
Table 6 (continued)
RegulationNodeDegreeBetweennessStressClosenessClustering coefficient
DownAHR430.00521120845560.3323330.013289
DownASNS430.00662816895420.3447040.011074
DownNEK2420.00638916009200.3328320.011614
DownTPX2410.005125022840.3301140.005398
DownFANCG400.00443614078820.3354190.037179
DownGUSB400.0075325615420.3267680
DownBIRC5400.0054418110800.3366160.019231
DownHMGB2390.00591719126680.3691380.047233
DownULK1390.00758721960480.3271870
DownIQGAP2390.00594923151860.3296010
DownTYMS390.00884212908420.3445640.006006
DownMAGED2370.00485515989340.3441680.015015
DownLGALS3360.00508613081580.3154540.001587
DownNOTCH2360.00679516295640.3274190.004762
DownIGFBP3350.0066715605200.3345160.026891
DownGMNN350.00617114158740.3354630.026891
DownUHRF1350.00253210219520.3440980.097479
DownSMYD2350.00543516253660.3058680.001681
DownPTTG1340.00271210902420.3380010.024955
DownRALGDS320.00527830468960.2905640
DownMAPKAPK5310.00527710748120.3310150.010753
DownPDCD4300.0025815359180.3294520
DownSMS300.00587813316160.3342080.009195
DownPPP1R13B300.00485214950460.3284110.011494
DownLAMB1300.00538513127740.3266420
DownFHOD1290.00533616738340.3300070.007389
DownPRC1270.0028669926220.3388560.07
DownHOMER1270.0069929792940.3252650.006667
DownTTK260.0038719535200.3339450.012308
DownCHAF1B268.92E-045504780.3437960.123077
DownRAI14250.0033018623000.3344720.01
DownKIAA0101250.0042949120540.3287080.006667
DownCDCA8240.003499122200.3300930.036232
DownSPAG5240.0055566632420.3333550.007246
DownCCNB2240.0048685889300.3363940.039855
DownTIMELESS240.00496210348120.3283050.014493
DownKIF11240.002626630880.3425250.025362
DownDPP4240.0059425253440.2728490.004329
DownHMMR230.0014726571400.3290690.01581
DownEXO1238.12E-045671300.3308650.059289
DownHIST1H2BJ230.0041156389960.3588640.023715
DownTGFA220.00455126384920.2808540
DownHIST1H2BL210.0014457221880.355980.02381
DownSPARC210.0016152973820.3196710.095238
DownRABEP2200.0025314897340.3328320.036842
DownPTPN3190.00193612814320.2915780
DownMYO10190.0017085246840.3344060.023392
DownCDCA5190.0035135624000.3336830.005848
DownCD3D190.0030055579400.3328980.017544
DownULK2190.00192211841980.2889970
DownPMAIP1180.0020057342660.3287290
Table 6 (continued)
RegulationNodeDegreeBetweennessStressClosenessClustering coefficient
DownRRM2180.0018886289020.3524570.084967
DownGRB14180.0022339552120.2870590
DownFBXO32180.0026956153160.3248090
DownHMGB3180.0020915102360.3246430
DownNR0B1170.001532852640.3325720.029412
DownCLDN1170.0027519680920.2743780
DownPHF17170.0012223663480.3315540.007353
DownANXA4170.0023875147860.3343620.022059
DownJAG1160.00234192600.3272720.025
DownFGG160.00257317523680.3054090.041667
DownDDX3Y160.0013343430240.3411480.008333
DownHIST1H2BO159.90E-042697420.3252860
DownMELK150.0022535113380.3253480
DownLIG1150.0012714092940.3257850
DownASPM150.0011853777100.3272720.009524
DownCOL3A1155.63E-04976960.2896710.028571
DownPLK2150.0022365437400.3276510
DownRAD51AP1140.0025453930460.2811020.030303
DownTXNIP140.00228210188200.3285170
DownADA140.0051954843380.333880.030303
DownNUDT1140.0014693947020.3254110
DownHHEX140.0032064746680.3248290
DownSTK36130.0026924474540.3252240
DownHIST1H2BD131.57E-041448420.3255150
DownBMF130.0017097270300.2457770
DownHMBOX1130.00201412688080.2960190
DownRHOBTB3130.0023212659500.3301570.076923
DownENC1126.21E-042563160.325390
DownHIST1H2BN121.97E-041307180.3244160
DownANGPT2120.0015762597680.3245190
DownGGH120.0010433029680.3255150
DownANLN126.12E-043008280.3265580
DownCCDC14120.0010114002320.3277980
DownPLAGL1121.69E-041543360.3252440
DownCDKN3119.33E-041402420.3331150.083333
DownPPP1R13L111.14E-041100840.3335520.109091
DownSEMG1110.0014656555000.3286650
DownROR1110.001473421520.3280090.018182
DownHLA-DRB4110.00159213355240.282380
DownRAB11FIP4110.0014652677640.3255150.054545
DownLAMA3100.0012219313800.2625120
DownKIF22107.41E-042044100.3249740
DownCAP2108.59E-042141180.3248710
DownHRK108.77E-043999880.2713230
DownCCNG290.0011072770060.3257230
DownCCL1990.0019892175400.3243740
DownCSRP2BP90.0019737632380.2833540
DownKCNK190.0020243478460.3250990
DownAMY2A90.00236512171060.2286110
DownIQSEC190.00158112390200.2729220
DownFCER1A90.00118426476440.2426390
Table 6 (continued)
RegulationNodeDegreeBetweennessStressClosenessClustering coefficient
DownLGALS294.38E-042502160.2778050
DownHIST1H2BH91.45E-04965220.3243330
DownKNTC190.0016212543280.3242090
DownGRIN2C80.0012738870860.2339570
DownMCM883.94E-0643040.2847480.214286
DownWNT5A80.0019922270640.3269560.035714
DownMYO5C86.32E-041717000.3339230.071429
DownSULT2A178.32E-0411501840.2797280
DownZNF13371.91E-041314560.2713230
DownRPS4Y177.04E-05849620.3245190
DownHLA-DQB170.001641928420.3243740
DownZNF30274.24E-043303640.2713660
DownNEK370.0015772107340.2690150
DownTMPO77.82E-05689780.2794050
DownSMCR770.0010491385080.3242920
DownDEPDC766.14E-05372740.3243950
DownIGLL164.77E-05175780.2579910.133333
DownMICB60.0014512165120.3250160
DownMICA61.62E-04256580.2621610
DownIDH269.97E-041912040.324560
DownRANBP1760.0019631989600.3239410
DownRHOBTB264.30E-041064220.2663010.133333
DownCDCA261.77E-041190640.3341640.266667
DownAMY1A60.0017638580420.2288780
DownMATN367.85E-0418954560.2311010
DownNPTX260.0015766338640.2614340
DownRAD54L67.24E-041038480.3271240.066667
DownMUC2057.85E-046027500.2037440
DownCKAP259.24E-05391340.3243120
DownAPOBEC3B56.39E-041344500.3241060
DownCXCL950.0011971383040.2188370
DownPLA2G1B50.0011832023840.2133820
DownLTB48.04E-042533900.2241050
DownHSD11B246.40E-0646640.2651360
DownMAT1A47.99E-04962080.3238590
DownTBC1D841.66E-04800920.3253270
DownLCN249.09E-05241740.2376350
DownFZD648.03E-041377720.3248920
DownZG16B44.54E-04736940.3242920
DownEML140.0011782655600.2203430
DownZNF26647.34E-04867280.3243120
DownSPRR1A47.91E-042650020.25660
DownCYP3A5411210
DownIGJ31.10E-04389480.3247880.333333
DownCOL5A239.68E-05221400.3246220.333333
DownMLF1IP34.55E-0617700.2472450.333333
DownOSBPL634.50E-05111940.255480
DownPOPDC231610
DownKLK133.93E-044948420.2286930
DownANKRD2333.98E-042033840.2393330
DownGRAMD1C34.31E-04611780.3238170
Table 6 (continued)
RegulationNodeDegreeBetweennessStressClosenessClustering coefficient
DownCDCA737.97E-05923420.3260770
DownDDIT4L33.94E-041398700.2097610
DownDONSON33.95E-05774000.3258270
DownSULF226.87E-0641840.3240230
DownDSCAM21.27E-0547620.3237760
DownPLXDC126.08E-05126180.3237760
DownCD99L221.88E-05487680.3252440
DownPRSS824.00E-0820.1754030
DownFAM54A22.80E-0633040.3238170
DownSTAG324.30E-074640.2387720
DownFANK129.60E-076820.2370820
DownZNF44324.29E-05164180.3237760
DownPNLIPRP221210
DownCTSL223.93E-04397960.3237760
DownZDHHC2323.93E-041665280.2457060
DownIER526.89E-0541700.2743930
DownCOL27A121.00E-07160.218790
DownLRIG323.93E-041935540.2567550
DownAMY2B21.13E-068340.2379910
DownESM123.93E-04663900.1980480
DownTPSAB121.10E-07680.2102810
DownTMEM441000.2353620
DownPALMD1000.2152490
DownKIAA140710010
DownGPX81000.3237350
DownCCDC1501000.2522040
DownPDE8B1000.3237350
DownRAD511000.2536730
DownST6GAL- NAC21000.2120050
DownCX3CR110010
DownAPOBEC3A1000.3237350
DownPCYOX1L1000.2401910
DownEXO11000.2669290
DownRNF441000.3237350
DownXYLT21000.2276510
DownSRCRB4D1000.2522040
DownRPS4Y21000.3237350
DownFUK1000.3237350
DownCep1921000.2460740
DownZNF7001000.3237350
DownHCP51000.2456830
DownCDH11000.2673490
DownSLC2A4RG1000.2436260
DownTIGD710010
DownHPGD1000.2456830
DownTCEA310010
DownIL20RB10010
DownZNF6181000.2339460
Table 6 (continued)
RegulationNodeDegreeBetweennessStressClosenessClustering coefficient
DownCCDC74A1000.2312270
DownPAQR41000.2522040
DownPAQR610010

interacts with 144 miRNAs. Meanwhile, top five down regu- lated targeted genes such as TXNIP interacts with 228 miR- NAs, MAPKAPK5 interacts with 179 miRNAs, PMAIP1 interacts with 147 miRNAs, RAD51 interacts with 147 miRNAs, and MICA interacts with 142 miRNAs (Table 7).

Construction of target genes-TF regulatory network

Target genes (up and down regulated) interacts with TF are shown Figs. 14 and 15. Top five up regulated targeted genes such as HSPA1A interacts with 67 TFs, PHOX2B interacts with 54 TFs, H19 interacts with 52 TFs, CEBPD interacts with 51 TFs, and DNAJC3 interacts with 50 TFs. Meanwhile, top five down regulated targeted genes such as F11R interacts with 91 TFs, CHAF1B interacts with 85 TFs, FANCG interacts with 82 TFs, CENPF interacts with 82 TFs, and XRCC1 interacts with 82 TFs (Table 8).

TCGA data of ACC patients are used via the UALCAN data portal. Kaplan-Meier curve for overall survival of TCGA patients with ACC is obtained according to the low and high expression of each gene. The results showed that patients in the high mRNA expression group for YWHAZ had worse overall survival than those in the low expression group (P=0.012) (Fig. 16a), the high mRNA expression group for STAT1 had worse overall survival than those in the low expression group (P=0.024) (Fig. 16b), the high mRNA expression group for ICAM1 had worse overall sur- vival than those in the low expression group (P=0.008) (Fig. 16c, a), the high mRNA expression group for SH3BP5 had worse overall survival than those in the low expression group (P=0.016) (Fig. 16d), the high mRNA expression group for CD83 had worse overall survival than those in

Fig. 7 Node degree distribution for up and down regulated genes. Red lines: regression lines

A

4000

3000

R square = 0.761

B

Correlation coefficient = 0.967

R square = 0.761

Correlation coefficient = 0.978

1000

1000

Number of nodes

Number of nodes

100

100

10

10

1

1

1

10

100

900

1

10

100

1000

2000

Degree

Degree

Fig. 6 Protein-protein interaction (PPI) networks for differentially- expressed genes (DEGs). (Pink round shape node represents down- regulated genes). Green dots are also genes which are not hub or dif- ferential expressed genes
Fig. 8 Regression diagrams for upregulated genes (a betweenness centrality; b stress centrality; c closeness centrality; d clustering coefficient). The red straight lines and the red curve lines: regression lines

A

1.05

B

4000

1.00

0.95

0.90

0.85

1000

0.80

0.75

Betweenness centrality

0.70

0.65

Number of nodes

·

0.60

0.55

R square = 0.602

100

0.50

0.45

Correlation coefficient = 0.105

0.40

0.35

0.30

R square = 0.001

10

0.25

Correlation coefficient = 0.111

0.20

0.15

0.10

0.05

0.00

1

0

50

100

150

200

250

300

350

400

450

500

550

600

650

700

750

800

1

1E1

1E2

1E3

1E4

1E5

1E6

1E7

1E8

Number of neighbors

Stress centrality

C

1.05

1.00

D

0.500

R.square =0.186

0.475

R square = 0.447

0.95

0.90

Correlation coefficient = 0.338

0.450

Correlation coefficient = 0.686

0.85

0.425

0.80

0.400

0.75

0.375

0.350

Closeness centrality

0.70

Avg. clustering coefficient

0.65

0.325

0.60

0.300

0.55

0.275

0.50

0.250

0.45

0.225

0.40

0.200

0.35

0.175

0.30

0.150

0.25

0.125

0.20

0.100

0.15

0.075

0.10

0.050

0.05

0.025

0.00

0.000

1

10

100

900

1

10

100

900

Number of neighbors

Number of neighbors

the low expression group (P=0.00016) (Fig. 16e), the high mRNA expression group for FN1 had worse overall sur- vival than those in the low expression group (P=0.0069) (Fig. 16f), the high mRNA expression group for TK1 had worse overall survival than those in the low expression group (P=0.0001) (Fig. 16g), the high mRNA expression group for HIST1H1C had worse overall survival than those in the low expression group (P=0.0057) (Fig. 16h), the high mRNA expression group for CABLES1 had worse overall survival than those in the low expression group (P=0.017) (Fig. 16i), and the high mRNA expression group for MCM3 had worse overall survival than those in the low expression group (P=0.00011) (Fig. 16j). TCGA data analysis showed that hub genes such as YWHAZ, STAT1, ICAM1, CD83, FN1, TK1, HIST1H1C, and MCM3 were highly expressed in stages 4 (Fig. 17), while hub genes such as SH3BP5 and CABLES1 were highly expressed in stages 2 and stages 1 (Fig. 18).

Genetical alteration of the five hub genes

Five hub genes’ alteration statuses in TCGA bladder cancer patients were analyzed using the CbioPortal database. The five hub genes such as YWHAZ, STAT1, SH3BP5, TK1,

and HIST1H1C altered in 0% patients, while five hub genes such as ICAM1, CD83, FN1, CABLES1, and MCM3 altered in 3% (missence mutation and amplification) and 1.1% (mis- sence mutation and amplification) patients and the frequency of alteration of each hub gene are shown in Fig. 19.

Discussion

In recent years, although the morbidity of ACC has less, it is still malignant tumors worldwide. Specific biomarkers and effective targets are still needed to be diagnosed.

In this study, a total of 884 DEGs were picked out from the profile of GSE19775, including 441 up regulated genes and 443 down regulated genes. Gene such as phenylethan- olamine N-methyltransferase (PNMT) [59] and cocaine- and amphetamine-regulated transcript (CART) [60] were associ- ated with development of adrenal pheochromocytoma, but these genes may be responsible for progression of ACC. Methylation inactivation of tumor suppressor gene proen- kephalin (PENK) was responsible for development of colo- rectal cancer [61], but inactivation of this gene may be iden- tified with growth of ACC. Chromogranin A (parathyroid secretory protein 1) (CHGA) was important for progression

Fig. 9 Regression diagrams for down-regulated genes (a betweenness centrality; b stress centrality; c closeness centrality; d clustering coeffi- cient). The red straight lines and the red curve lines: regression lines Fig. 10 Modules in PPI net- work. The pink round nodes denote down-regulated genes. Green dots are also genes which are not hub or differential expressed genes

A

1.05

B

3000

1.00

R square = 0.011

0.95

0.90

1000

Correlation coefficient = 0.090

0.85

0.80

0.75

Betweenness centrality

0.70

0.65

Number of nodes

0.60

100

0.55

R square =0.574

0.50

0.45

Correlation coefficient = 0.109

0.40

0.35

0.30

10

0.25

0.20

0.15

0.10

0.05

0.00

1

0

100

200

300

400

500

600

700

800

900

1000

1

1E1

1E2

1E3

1E4

1E5

1E6

1E7

1E8

Number of neighbors

Stress centrality

C

1.05

R square = 0.198

D

1.00

0.325

Correlation coefficient = 0.293

R square = 0.663

0.95

0.90

0.300

Correlation coefficient = 0.810

0.85

0.80

0.275

0.75

0.250

Closeness centrality

0.70

Avg. clustering coefficient

0.65

0.225

0.60

0.200

0.55

0.50

0.175

0.45

0.150

0.40

0.35

0.125

0.30

| !. ..

0.100

0.25

0.20

0.075

0.15

0.050

0.10

0.05

0.025

0.00

0.000

1

10

100

1000

2000

1

10

100

1000

2000

Number of neighbors

Number of neighbors

Module 6

Module 30

MYH10

CFL1

COPS

MYBBPLA

PRKDC

HSPGOA

GRK5

ANKİ

HES1

UBC

ZNF331

GK

MED

MADD

DOB1

KPNB

NCL

EEF2

DHX9

PSMD

PTBNÍ

GINS4

WHAG

TEFIAT

HSP90AB1

USP9

CALF

SIRT1

PNIN

BCR

NR4A1

ŞRSF

IF4A

BXA2

SAPI

AV

ARP1

HSPA4

ALM

NOLC

WHAZ

YWHAZ

ID2

YWHAG

PTAN

OLA1

BTK38

STAT3

P36578

UBC

MYHR

UVBL

DHX15

HNRNPO

PPFIBP

WHAB

SRRM2

EIF3A

MRPS27

Module 37

Module 55

FN1

STAT1

YAP1

APOC

SERPING1

C1S

UBC

IPO7

HP

VPS26A

APOE SH3BP5 PLAT

HSPA4L

APEH

Module 2

Module 8

Fig. 11 Modules in PPI net- work. The pink round nodes denote down-regulated genes. Green dots are also genes which are not hub or differential expressed genes

PCNA

AIRE

TGA

ICM

CAP

ACLY

DBF4

PROAB

SFJ8

UMO

SAP

LADS

EFIA

INCR

MCM6

MCM2

CNO

ORC

UVB

JBC

MS22

PAI

AND

PEX

NG5

ST4H

ACM

FN1

CAM

MCM3

RABBE

UVEILZ

SPA1

HDAC

IST3H

ONS

EEF2

MORF4

DKN2

CMT

PORFAL

GINS

VIGM

DRCZ

NTN2

ORCE

3MBTL

ORC

PRKDC

DDX5

CAND1

UBC

NONO

PIAS1

NRNPC

WHA

INRNP

(2AF)

NCL

YBX1

SFPQ

RNP

FBL

NRNP2

12AF

WHAO

PRPFB

OP2

IRNPA

RCCE

HIST1H

UMO2

DHXS

F3B

UBD

RNF2

RMTS KPNB1

MAD2L PHGDP

MAGED2 2

ODX1

HNRNPA2B1

Module 10

Fig. 12 The network of upregu- lated DEGs and their related miRNAs. The yellow circle nodes are the down-regulated target gene and blue diamond nodes are miRNAs. Black lines means interaction with adjutant genes or miRNAs

GADDISA

PAN2

ING2

MCM3

JHRF

MCM6

RFCA

FN1

PBK

ISPB

NMT

IST4H

PHGDH

ASNS

TMPO

COK1

MCM2

CAM

CHAF1

TYMS

TOP2A

HIST 1H2BL

HIST1H1C

HMGB2

LBC

HIST1H2BJ

ICOR2

ST1H2BC

Module 27

CDK1

UBC

CDK2

CUL4B

TP73

POLD

SKP2

NRF1

CDT1

PRC1

CCNE

CDC6

CUL4A

CDK4

CUL1

CDC5L

E2F1

of gastroenteropancreatic neuroendocrine tumors [62], but this gene may be diagnosed with development of ACC. Genes such as FGF23 [63] and NEK3 [64] were liable for invasion of prostate cancer cells, but these genes may be

associated with invasion of ACC cells. Single nucleotide polymorphism (SNP) in SLC2A4RG was linked with devel- opment of glioblastoma [65], but SNP in this gene may be liable for advancement of ACC. Alteration in CHTF18 was

Fig. 13 The network of down- regulated DEGs and their related miRNAs. The red circle nodes are the down-regulated target gene and blue diamond nodes are miRNAs. Black lines means interaction with adjutant genes or miRNAs

linked with development of endometrial cancer [66], but mutation in this gene may be responsible for pathogenesis of ACC. HMGB2 was identified with development chemore- sistance in gastric cancer [67], but this gene may be respon- sible for drug resistance in ACC. EZH2 was reasonable for pathogenesis of ACC [68].

In pathway enrichment analysis, up regulated genes were mainly associated with several pathways from different path- way databases (BIOCYC, KEGG, PID, REACTOME, Gen- MAPP, MSigDB C2 BIOCARTA, PantherDB, and SMPDB) such as catecholamine biosynthesis, aldosterone synthesis and secretion, IL6-mediated signaling events, metallothio- neins bind metals, steroid hormone metabolism, ensemble of genes encoding extracellular matrix and extracellular matrix-associated proteins, dopamine receptor mediated signaling pathway, and leptin system. SNP in genes such as CYP11A1 [69], HSD3B1 [70], SCARB1 [71], lumican (LUM) [72], and IRS1 [73] were liable for progression of different cancers such as colorectal cancer, prostate cancer, thyroid cancer and breast cancer, but SNP in these genes may be involved in development of ACC. Gene such as CYP11B2 [74], HSD3B2 [75], STAT3 [76], CYP17A1 [77], CCN3 [78], IGFBP2 [79], IGFBP5 [80], IGFBP6 [80], and PRKAR2B [81] were diagnosed with growth of ACC. Genes such as MC2R [82], CCAAT/enhancer binding

protein (C/EBP), beta (CEBPB) [83], and ANGPTL4 [84] were involved in proliferation of different cancer cells such as prostate cancer, breast cancer, and colorectal cancer, but these genes may be associated with proliferation of ACC cells. Gene such as NR4A1 [85], NR4A2 [86], PRKD3 [87], ADAMTS1 [88], CCL13 [89], CRLF1 [90], CXCL12 [91], CXCL2 [92], decorin (DCN) [93], FGF9 [94], GDF15 [95], plasminogen activator, tissue (PLAT) [96], S100A8 [97], S100A9 [97], SEMA6A [98], SRPX2 [99], and tenascin XB (TNXB) [100] were important for invasion of different cancer cells such as breast cancer, colorectal cancer, prostate cancer, thyroid cancer, ovarian cancer, endometrial cancer, gastric cancer, glioblastoma, and mesothelioma, but these genes may be linked with invasion of ACC cells. IL6 was responsible for inflammation in breast cancer [101], but this gene may be linked with inflammation in ACC. High expression of jun B proto-oncogene (JUNB) [102], STAT1 [103], MT1E [104], FGF7 [105], fibromodulin (FMOD) [106], SPON2 [107], and THBS1 [108] were important for advancement of different cancers such as renal cancer, colon cancer, breast cancer, prostate cancer and esophageal squa- mous cell carcinoma, but high expression of these genes may be identified with growth of ACC. Methylation inactivation of tumor suppressor genes such as SOCS3 [109], MT1G [110], MT1H [111], ADAMTS9 [112], ANGPTL1 [113],

Table 7 Target gene-miRNA interaction table
RegulationTarget geneDegreeMicroRNARegulationTarget geneDegreeMicroRNA
UpYWHAZ212hsa-mir-3662DownTXNIP228hsa-mir-6845-5p
UpGATA6207hsa-mir-4273DownMAPKAPK5179hsa-mir-548az-3p
UpLDLR167hsa-mir-4666a-3pDownPMAIP1147hsa-mir-4316
UpBZW1149hsa-mir-548uDownRAD51147hsa-mir-6722-3p
UpIGFBP5144hsa-mir-5703DownMICA142hsa-mir-6808-5p
UpHSPA4L141hsa-mir-6879-3pDownMRNIP124hsa-mir-4722-5p
UpPEG10138hsa-mir-4443DownDYRK2118hsa-mir-3689a-3p
UpPTP4A1135hsa-mir-548ad-5pDownFZD6115hsa-mir-2113
UpMAT2A112hsa-mir-3689a-3pDownHIST1H2BD112hsa-mir-548bb-5p
UpDNAJB999hsa-mir-410-3pDownRACGAP1112hsa-mir-5698
UpCPE98hsa-mir-6511a-5pDownHOXA13111hsa-mir-6837-3p
UpTHBS195hsa-mir-4441DownCPM111hsa-mir-6771-5p
UpKCNK595hsa-mir-7977DownRRM2101hsa-mir-548ah-5p
UpFOSL294hsa-mir-1827DownRAB11FIP4100hsa-mir-208b-5p
UpATP1B389hsa-mir-520 hDownNR3C1100hsa-mir-6849-3p
UpFOXK284hsa-mir-4743-3pDownZWINT98hsa-mir-4421
UpAS3MT81hsa-mir-5690DownCOL1A197hsa-mir-4779
UpSTAT380hsa-mir-500b-3pDownTP53INP194hsa-mir-6853-3p
UpNDRG180hsa-mir-512-3pDownHMGB289hsa-mir-548az-5p
UpUNC5B79hsa-mir-550a-3-5pDownVCAM186hsa-mir-6884-5p
UpADM77hsa-mir-3121-3pDownIER585hsa-mir-4659b-3p
UpRAB2172hsa-mir-3126-3pDownCCNB184hsa-mir-548am-5p
UpNPTX169hsa-mir-3145-5pDownCHST681hsa-mir-5589-5p
UpSLC16A969hsa-mir-548pDownHMBOX181hsa-mir-548ar-5p
UpSF169hsa-mir-4294DownMCM880hsa-mir-4711-3p
UpTGFBR367hsa-mir-548ah-3pDownCHAF1B79hsa-mir-7703
UpBHMT267hsa-mir-4707-3pDownBIRC578hsa-mir-4716-5p
UpHOXA964hsa-mir-548 mDownPDCD478hsa-mir-6747-3p
UpCREBL263hsa-mir-548awDownPSAT177hsa-mir-548z
UpMSI261hsa-mir-6500-5pDownMELK74hsa-mir-4701-3p
UpPDGFRA61hsa-mir-548aq-3pDownMYO1074hsa-mir-4524a-3p
UpNRXN361hsa-mir-4768-3pDownHIST1H2BJ73hsa-mir-5697
UpCGNL161hsa-mir-6884-5pDownBBC373hsa-mir-4649-3p
UpMC2R59hsa-mir-676-5pDownAHR71hsa-mir-3689b-3p
UpSOAT157hsa-mir-6893-5pDownULK271hsa-mir-6847-3p
UpPGM356hsa-mir-7844-5pDownZBED367hsa-mir-3650
UpPSD356hsa-mir-520eDownBUB167hsa-mir-6878-5p
UpSLC33A155hsa-mir-508-5pDownHRK66hsa-mir-6755-5p
UpCEBPB54hsa-mir-185-5pDownNCOR264hsa-mir-6757-5p
UpSH3BP554hsa-mir-6504-3pDownCD3D64hsa-mir-6788-5p
UpELL254hsa-mir-548av-3pDownGALNT1064hsa-mir-211-5p
UpIPO753hsa-mir-101-3pDownRHOBTB363hsa-mir-3925-5p
UpZBED151hsa-mir-520bDownULK161hsa-mir-4483
UpERN150hsa-mir-4768-3pDownFANCA60hsa-mir-520a-3p
UpNOLC149hsa-mir-3529-3pDownTIMELESS60hsa-mir-2682-3p
UpZRANB148hsa-mir-548f-3pDownRNF4458hsa-mir-16-2-3p
UpSLC2A347hsa-mir-6838-5pDownOGT58hsa-mir-4270
UpCHSY147hsa-mir-5197-5pDownMICB56hsa-mir-3689c
UpFJX147hsa-mir-5590-3pDownNOTCH255hsa-mir-5100
UpSLC1A247hsa-mir-7977DownSRGAP250hsa-mir-204-3p
Table 7 (continued)
RegulationTarget geneDegreeMicroRNARegulationTarget geneDegreeMicroRNA
UpKCNK346hsa-mir-4296DownCDT148hsa-mir-550b-2-5p
UpARHGAP1845hsa-mir-4439DownSMS48hsa-mir-6511a-5p
UpHOXA744hsa-mir-3132DownE2F845hsa-let-7f-2-3p
UpEPB41L144hsa-mir-4510DownMYBL245hsa-mir-3184-5p
UpDHCR2443hsa-mir-532-3pDownTK145hsa-mir-6888-5p
UpHSPA542hsa-mir-5688DownEZH244hsa-mir-3679-3p
UpGABARAPL141hsa-mir-6867-3pDownOIP544hsa-mir-5690
UpPLA2G4A41hsa-mir-2115-3pDownLRIG343hsa-mir-7154-5p
UpSERP141hsa-mir-653-5pDownMAT1A43hsa-mir-5591-5p
UpMT1A41hsa-mir-6749-3pDownHIST1H2BF42hsa-mir-22-5p
UpSRPX240hsa-mir-2052DownMUC2042hsa-mir-3664-3p
UpIRS139hsa-mir-4676-3pDownCABLES140hsa-mir-548ae-3p
UpFZD438hsa-mir-4433a-3pDownMATN340hsa-mir-6893-5p
UpTFAP2B38hsa-mir-128-1-5pDownDDR140hsa-mir-199a-5p
UpDKK338hsa-mir-6734-3pDownTRIM4540hsa-mir-548x-3p
UpSERPING138hsa-mir-519e-5pDownDNMT139hsa-mir-377-3p
UpSIRT137hsa-mir-449b-5pDownTMEM4439hsa-mir-374b-3p
UpPRKAR1A37hsa-mir-548az-5pDownTIGD239hsa-mir-5197-5p
UpHOXA535hsa-mir-1909-5pDownPRSS838hsa-mir-1203
UpRAB3434hsa-mir-7113-5pDownTGFA38hsa-mir-5001-3p
UpICAM134hsa-mir-4643DownCLDN135hsa-mir-548u
UpIER334hsa-mir-7977DownNPTX235hsa-mir-4300
UpPRKD334hsa-mir-4773DownCCNE134hsa-mir-6838-5p
UpCYB56134hsa-mir-548aj-5pDownWNT5A32hsa-mir-516a-3p
UpPCK133hsa-mir-3650DownOSBPL331hsa-mir-6890-3p
UpSOCS332hsa-mir-8062DownUBD31hsa-mir-6886-3p
UpLITAF32hsa-mir-548anDownHMGB330hsa-mir-520 g-3p
UpALDH1A332hsa-mir-4533DownKCNK130hsa-mir-603
UpRPRM32hsa-mir-6827-5pDownIQSEC129hsa-mir-4436b-3p
UpTAGLN31hsa-mir-9-5pDownTMPO29hsa-mir-409-3p
UpID231hsa-mir-548t-5pDownJAG127hsa-mir-4282
UpGTPBP430hsa-mir-6870-3pDownCDCA827hsa-mir-6880-5p
UpFGF929hsa-mir-1279DownF11R27hsa-mir-6499-3p
UpNR4A329hsa-mir-4776-3pDownKNTC127hsa-mir-5584-3p
UpCEBPD28hsa-mir-6872-5pDownPTPN326hsa-mir-4731-3p
UpJUNB28hsa-mir-3960DownSLPI26hsa-mir-361-5p
UpNKAIN128hsa-mir-1255b-5pDownPPP1R13L26hsa-mir-9500
UpCNN327hsa-mir-888-5pDownZNF44325hsa-mir-7856-5p
UpZNF33127hsa-mir-3187-5pDownKIT25hsa-mir-4504
UpNEDD926hsa-mir-5702DownGPX825hsa-mir-6833-3p
UpECHDC326hsa-mir-4717-5pDownTCEA324hsa-mir-1233-3p
UpPON126hsa-mir-1273 g-3pDownHIST1H2BO24hsa-mir-8057
UpQPCT25hsa-mir-7703DownDDX3Y23hsa-mir-548at-5p
UpDNAJC324hsa-mir-548av-5pDownPOPDC223hsa-mir-612
UpTPMT24hsa-mir-5089-5pDownSLC2A4RG23hsa-mir-6787-5p
UpGEM24hsa-mir-5093DownHIST1H1C22hsa-mir-3940-5p
UpADAMTS924hsa-mir-548ah-5pDownCDCA722hsa-mir-3606-3p
UpCDH224hsa-mir-208b-5pDownDMTF122hsa-mir-644a
UpSTARD1324hsa-mir-219a-1-3pDownZNF61822hsa-mir-548 s
UpSAA124hsa-mir-4651DownCDH122hsa-mir-203a-3p
Table 7 (continued)
RegulationTarget geneDegreeMicroRNARegulationTarget geneDegreeMicroRNA
UpADH1B24hsa-mir-300DownPRSS1622hsa-mir-3135b
UpVASN23hsa-mir-4254DownSERPINA322hsa-mir-6500-3p
UpSNAI123hsa-mir-506-3pDownAPOBEC3A22hsa-mir-212-5p
UpSEMA6A23hsa-mir-506-3pDownZSWIM922hsa-mir-208a-5p
UpFDX123hsa-mir-3653-5pDownMMP921hsa-mir-211-5p
UpGDF1523hsa-mir-3681-3pDownGMNN21hsa-mir-7847-3p
UpSPON223hsa-mir-3150a-3pDownFGG21hsa-mir-6780b-3p
UpIL622hsa-let-7f-5pDownSPARC21hsa-mir-767-5p
UpHAND222hsa-mir-7111-5pDownPTCD120hsa-mir-5580-5p
UpSFPQ22hsa-mir-1229-3pDownDAND520hsa-mir-7703
UpCYP26B121hsa-mir-4524a-5pDownPLXDC120hsa-mir-3121-3p
UpGJA121hsa-mir-200a-3pDownCCDC1419hsa-mir-4302
UpMT1E21hsa-mir-4677-5pDownTBC1D819hsa-mir-7849-3p
UpDUSP521hsa-mir-16-1-3pDownDONSON19hsa-mir-5089-3p
UpFRMD521hsa-mir-548bb-3pDownHIST1H2BE19hsa-mir-299-5p
UpCYP11A121hsa-mir-4709-3pDownRFC519hsa-mir-188-3p
UpFGF720hsa-mir-302d-3pDownHIST1H2BN19hsa-mir-4252
UpMAP3K520hsa-mir-642b-3pDownCDKN318hsa-mir-1307-3p
UpCXCL1220hsa-mir-7152-3pDownHIST1H2BB18hsa-mir-3940-5p
UpSTAT119hsa-mir-1183DownCKAP217hsa-mir-3609
UpCREM18hsa-mir-3117-3pDownTOP2A17hsa-mir-5688
UpGCLM18hsa-mir-6131DownMAD2L117hsa-mir-3978
UpPAPSS218hsa-mir-297DownPHGDH17hsa-mir-6792-5p
UpCTH18hsa-mir-4470DownPRC117hsa-mir-5692a
UpTIPARP18hsa-mir-4680-5pDownHIST1H2BL17hsa-mir-6839-3p
UpMRAS18hsa-mir-2392DownCYP3A517hsa-mir-3690
UpACVR1C17hsa-mir-376b-3pDownANKRD2317hsa-mir-3960
UpCRLF117hsa-mir-377-3pDownIDH216hsa-mir-1250-3p
UpMTSS117hsa-mir-6769b-3pDownANGPTL215hsa-mir-4789-5p
UpGPM6B16hsa-mir-3919DownGADD45A15hsa-mir-135b-3p
UpFUBP116hsa-mir-222-3pDownNEK315hsa-mir-548e-3p
UpNR4A216hsa-mir-520f-5pDownHIST1H4H15hsa-mir-4796-3p
UpFBLN516hsa-mir-200c-3pDownFABP315hsa-mir-3907
UpAOC316hsa-mir-6800-5pDownUHRF114hsa-mir-191-5p
UpP2RY216hsa-mir-6511a-3pDownZNF60614hsa-mir-653-3p
UpGALC15hsa-mir-3606-3pDownSMYD214hsa-mir-5588-3p
UpSYT415hsa-mir-106b-5pDownDNMT3B14hsa-mir-506-3p
UpRASD115hsa-mir-3180DownMCM314hsa-mir-1260b
UpCD3815hsa-mir-4659a-5pDownHIST1H2BH14hsa-mir-5693
UpSCARB114hsa-mir-3121-5pDownTYMS13hsa-mir-99a-5p
UpADAMTS113hsa-mir-6854-3pDownKIF1113hsa-mir-340-5p
UpHES112hsa-mir-765DownZNF26613hsa-mir-4262
UpENPP212hsa-mir-17-3pDownCHAF1A12hsa-mir-20b-5p
UpABCB112hsa-mir-508-5pDownCENPF12hsa-mir-122-5p
UpHSPA1A11hsa-mir-223-5pDownIGFBP312hsa-mir-210-3p
UpNBEA11hsa-mir-18a-5pDownCOL4A512hsa-mir-802
UpSCN7A11hsa-mir-3675-3pDownPNMA312hsa-mir-6792-3p
UpXBP110hsa-mir-320cDownCOL14A112hsa-mir-548an
UpCCL210hsa-let-7 g-3pDownCOL3A111hsa-mir-29b-1-5p
UpC1S10hsa-mir-4778-3pDownRPS4Y111hsa-mir-208b-3p
Table 7 (continued)
RegulationTarget geneDegreeMicroRNARegulationTarget geneDegreeMicroRNA
UpTMEM13010hsa-mir-644aDownPLK211hsa-mir-190a-3p
UpPHOX2B10hsa-mir-181d-5pDownZDHHC2311hsa-mir-4668-3p
UpGNAZ10hsa-mir-5587-5pDownSULF211hsa-mir-4439
UpAADAC10hsa-mir-8062DownRAD51AP110hsa-mir-18b-5p
UpLRRC3810hsa-mir-1228-3pDownKIAA1324L10hsa-mir-6832-3p
UpC710hsa-mir-1245b-3pDownMCM210hsa-mir-500a-5p
UpCYP11B29hsa-mir-4666bDownFHOD110hsa-mir-4789-3p
UpHSD3B19hsa-mir-500a-5pDownMYO5C10hsa-mir-6512-3p
UpFGF239hsa-mir-548az-5pDownBARD110hsa-mir-6501-3p
UpDUSP169hsa-mir-892aDownENC110hsa-mir-505-5p
UpRND38hsa-mir-200b-3pDownHOMER19hsa-mir-5010-3p
UpFCN28hsa-mir-5589-3pDownPPP1R13B9hsa-mir-29c-3p
UpEGR18hsa-mir-181a-5pDownGRAMD1C9hsa-mir-3200-5p
UpCASP97hsa-let-7a-5pDownPTTG18hsa-mir-146a-3p
UpPHF107hsa-mir-409-3pDownXYLT28hsa-mir-18a-5p
UpS100A97hsa-mir-1204DownMSH28hsa-mir-15a-5p
UpSNAPC17hsa-mir-4742-3pDownHIST1H2BC8hsa-mir-296-3p
UpNR4A16hsa-let-7d-5pDownNCOA68hsa-mir-33a-5p
UpCTSD6hsa-mir-339-5pDownROR18hsa-mir-3922-3p
UpPDK46hsa-mir-103a-3pDownFN18hsa-mir-200c-3p
UpKCTD146hsa-mir-27a-3pDownRNFT28hsa-mir-922
UpGRK56hsa-mir-1238-5pDownIQGAP28hsa-mir-208a-3p
UpCALD15hsa-mir-15a-5pDownANXA48hsa-mir-7161-5p
UpTBX35hsa-mir-206DownXRCC18hsa-mir-5700
UpUCHL15hsa-mir-218-5pDownCOL27A18hsa-mir-6757-5p
UpCXCL25hsa-mir-532-5pDownCCDC74A8hsa-mir-411-3p
UpSYT135hsa-mir-6743-5pDownSTK368hsa-mir-8485
UpHEPH5hsa-mir-3613-3pDownASNS7hsa-mir-17-5p
UpSLC25A194hsa-let-7b-5pDownCOL5A27hsa-mir-222-3p
UpHOXB24hsa-mir-4762-5pDownHPGD7hsa-mir-664a-3p
UpABR4hsa-mir-93-3pDownTTK7hsa-mir-376a-5p
UpFGF124hsa-mir-4668-5pDownOSBPL67hsa-mir-4477b
UpTNFRSF11B4hsa-mir-181b-5pDownNEK27hsa-mir-4668-5p
UpTESK14hsa-mir-32-5pDownFBXO327hsa-mir-4647
UpATP5L4hsa-mir-100-5pDownESM17hsa-mir-1260a
UpANGPTL44hsa-mir-29b-3pDownASPM6hsa-let-7a-5p
UpCD834hsa-mir-373-3pDownPOLD16hsa-let-7e-5p
UpSCAP4hsa-mir-10a-5pDownLAMB16hsa-mir-760
UpIGFBP24hsa-mir-204-5pDownHCP56hsa-mir-519d-3p
UpTMEM254hsa-mir-636DownRAI146hsa-mir-423-3p
UpTMOD14hsa-mir-1185-1-3pDownKIF226hsa-mir-25-5p
UpNPC13hsa-mir-33a-5pDownMCM66hsa-mir-1180-3p
UpRAB383hsa-mir-30a-5pDownCD99L26hsa-mir-3064-3p
UpPLAT3hsa-mir-21-5pDownCDCA26hsa-mir-5586-5p
UpPTX33hsa-mir-224-5pDownSUCNR16hsa-mir-4501
UpS100A83hsa-mir-125b-5pDownCCNB25hsa-let-7f-5p
UpNFIL33hsa-mir-183-5pDownTCFL55hsa-mir-331-3p
UpMT1F3hsa-mir-219a-5pDownANKRA25hsa-mir-30a-5p
UpAPOE3hsa-mir-1908-5pDownCCNG25hsa-mir-93-3p
UpSDF2L13hsa-mir-30c-5pDownHMMR5hsa-mir-98-5p
Table 7 (continued)
RegulationTarget geneDegreeMicroRNARegulationTarget geneDegreeMicroRNA
UpALDH3A23hsa-mir-155-5pDownEML15hsa-mir-1229-3p
UpAKR1B13hsa-mir-342-5pDownANLN5hsa-mir-503-5p
UpDLL13hsa-mir-130b-3pDownKIF245hsa-mir-7-5p
UpCXCL13hsa-mir-27b-5pDownBMF5hsa-mir-34c-5p
UpNEFH3hsa-mir-142-3pDownRALGDS5hsa-mir-374a-5p
UpIFI273hsa-mir-502-5pDownSPAG55hsa-mir-539-5p
UpFMOD2hsa-mir-124-3pDownPBK5hsa-mir-216b-5p
UpSLC27A62hsa-mir-26b-5pDownPCYOX1L5hsa-mir-5002-3p
UpPDE8A2hsa-mir-33a-5pDownNTN44hsa-mir-196a-5p
UpMGST12hsa-mir-652-3pDownGUSB4hsa-mir-449b-3p
UpMT1X2hsa-mir-1225-3pDownCD694hsa-mir-32-5p
UpFNDC42hsa-mir-7-5pDownCDCA53hsa-mir-18b-5p
UpGK2hsa-mir-132-3pDownFANCG3hsa-mir-744-5p
UpALDH1A12hsa-mir-140-5pDownBRD83hsa-mir-24-3p
UpNR2F12hsa-mir-181b-5pDownDDB23hsa-mir-675-5p
UpTCEAL72hsa-mir-182-5pDownLIG13hsa-mir-149-5p
UpMFAP42hsa-mir-449aDownCXCL93hsa-mir-26b-5p
UpPLEK22hsa-mir-138-5pDownHSPB73hsa-mir-124-3p
UpPC2hsa-mir-125a-5pDownTHOC33hsa-mir-27a-3p
UpMAPK42hsa-mir-127-3pDownFUK3hsa-mir-92a-3p
UpABTB22hsa-mir-106b-5pDownADA3hsa-mir-140-5p
UpDLG22hsa-mir-148b-3pDownRFC43hsa-mir-193b-3p
UpALAS12hsa-mir-423-3pDownERICH53hsa-mir-215-5p
UpAASS2hsa-mir-591DownANGPT23hsa-mir-542-3p
UpGPRASP12hsa-mir-3140-3pDownLGALS33hsa-mir-744-5p
UpCDH181hsa-let-7e-5pDownCCL193hsa-mir-9-5p
UpAOX11hsa-mir-26b-5pDownEXO13hsa-mir-30e-5p
UpFMO31hsa-mir-26b-5pDownCHTF183hsa-mir-378a-5p
UpGSTT21hsa-mir-26b-5pDownHHEX2hsa-mir-19b-3p
UpPNMT1hsa-mir-26b-5pDownSULT2A12hsa-mir-24-3p
UpIL1R21hsa-mir-26b-5pDownHIST1H4J2hsa-mir-26a-5p
UpCH25H1hsa-mir-26b-5pDownDFNA52hsa-mir-1-3p
UpIL1RL11hsa-mir-26b-5pDownLAMA32hsa-mir-181a-5p
UpDNAJC121hsa-mir-26b-5pDownHIST1H2BI2hsa-mir-98-5p
UpFBLN11hsa-mir-30a-3pDownPAQR62hsa-mir-335-5p
UpHBB1hsa-mir-92a-3pDownPAQR42hsa-mir-96-5p
UpLXN1hsa-mir-92a-3pDownKIF18A2hsa-mir-192-5p
UpSCG21hsa-mir-98-5pDownCCDC1502hsa-mir-215-5p
UpCHGA1hsa-mir-107DownZNF7002hsa-mir-425-5p
UpMGAT21hsa-mir-30c-5pDownRHOBTB22hsa-mir-106b-5p
UpSLCO2A11hsa-mir-181a-5pDownPNLIPRP22hsa-mir-148b-3p
UpTH1hsa-mir-1-3pDownMAGED22hsa-mir-877-3p
UpRGN1hsa-mir-1-3pDownPOSTN1hsa-let-7f-5p
UpPI161hsa-mir-1-3pDownGRB141hsa-mir-26b-5p
UpECE21hsa-mir-124-3pDownSPRR1A1hsa-mir-26b-5p
UpCLDN51hsa-mir-128-3pDownZNF1331hsa-mir-26b-5p
UpADH1A1hsa-mir-132-3pDownRAD54L1hsa-mir-26b-5p
UpKCNQ11hsa-mir-133a-3pDownLY6D1hsa-mir-26b-5p
UpCRH1hsa-mir-142-3pDownGGH1hsa-mir-26b-5p
UpDDC1hsa-mir-145-5pDownNUP1071hsa-mir-93-5p
Table 7 (continued)
RegulationTarget geneDegreeMicroRNARegulationTarget geneDegreeMicroRNA
UpGSTA41hsa-mir-185-5pDownPLAGL11hsa-mir-98-5p
UpCHGB1hsa-mir-375DownPALMD1hsa-mir-98-5p
UpAQP111hsa-mir-375DownZNF3021hsa-mir-197-3p
UpNAP1L51hsa-mir-381-3pDownTAF1C1hsa-mir-30d-5p
UpAPOC11hsa-mir-335-5pDownHIST1H4F1hsa-mir-34a-5p
UpCYP21A21hsa-mir-335-5pDownHIST1H4K1hsa-mir-34a-5p
UpDBH1hsa-mir-335-5pDownDEPDC71hsa-mir-132-3p
UpHSD3B21hsa-mir-335-5pDownLCN21hsa-mir-138-5p
UpNPY1hsa-mir-335-5pDownNUDT11hsa-mir-145-5p
UpNPY1R1hsa-mir-335-5pDownRANBP171hsa-mir-361-5p
UpRARRES21hsa-mir-335-5pDownZNF4041hsa-mir-375
UpSEMA3B1hsa-mir-335-5pDownRABEP21hsa-mir-378a-3p
UpCDH191hsa-mir-335-5pDownPDE8B1hsa-mir-335-5p
UpSCG31hsa-mir-335-5pDownZG16B1hsa-mir-335-5p
UpGIPC21hsa-mir-335-5pDownCCDC1121hsa-mir-335-5p
UpAK71hsa-mir-335-5pDownOR8U11hsa-mir-146b-5p
UpSTARD61hsa-mir-335-5pDownITPKA1hsa-mir-193b-3p
UpARHGAP361hsa-mir-335-5pDownAPOBEC3B1hsa-mir-193b-3p
UpARFGAP31hsa-mir-93-3pDownTPX21hsa-mir-193b-3p
UpEFEMP11hsa-mir-338-5pDownNR0B11hsa-mir-561-3p
UpPRKAR2B1hsa-mir-590-3pDownCAP21hsa-mir-605-5p
UpANGPTL11hsa-mir-921DownCX3CR11hsa-mir-296-3p
UpTNXB1hsa-mir-1301-3pDownDEF61hsa-mir-3662
UpATP4A1hsa-mir-1289

Degree-no of miRNA interact with target gene. We taken any one miRNA in table

FBLN1 [114], FCN2 [115], SEMA3B [116], and TIMP4 [117] were diagnosed with growth of different cancers such as prostate cancer, gastric cancer hepatocellular carcinoma, and lung cancer, but loss of these genes may be responsi- ble for pathogenesis of ACC. Decrease expression of tumor suppressor gene MT1F was liable for progression of hepa- tocellular carcinoma [118], but less expression of this gene may be identified with growth of ACC. Genes such as CCL2 [119], CXCL1 [120], and EFEMP1 [121] were associated with angiogenesis in different cancers such as breast cancer and colorectal cancer, but these genes may be linked with angiogenesis in ACC. Tyrosine hydroxylase (TH) [122] and neuropeptide Y (NPY) [123] were responsible for patho- genesis of pheochromocytoma, but these genes may be associated with development of ACC. Dopa decarboxylase (aromatic L-amino acid decarboxylase) (DDC), CYP21A2, KCNK3, low density lipoprotein receptor (LDLR), CCAAT/ enhancer binding protein (C/EBP), delta (CEBPD), MT1A, MT1B, MT1X, CTSD, FBLN5, FGF12, MFAP4, SERP- ING1, SPOCK3, dopamine beta-hydroxylase (dopamine beta-monooxygenase) (DBH) EPB41L1 and guanine nucleotide binding protein (G protein), alpha z polypeptide (GNAZ) were novel biomarkers for pathogenesis of ACC

in these pathways. Meanwhile down regulated genes were mainly associated with several pathways from different path- way databases such as pyrimidine deoxyribonucleosides sal- vage, systemic lupus erythematosus, FOXM1 transcription factor network, SIRT1 negatively regulates rRNA expres- sion, methionine metabolism, CDK regulation of DNA rep- lication, integrin signaling pathway, mismatch repair path- way, and adenosine deaminase deficiency. High expression of genes such as TK1 [124], thymidylatesynthetase (TYMS) [125], CCNE1 [126], CDT1 [127], FN1 [128], NTN4 [129], and adenosine deaminase (ADA) [130] were associated with pathogenesis of different cancer such as breast cancer, colorectal cancer, ovarian cancer, and prostate cancer, but elevated expression of these genes may be liable for devel- opment of ACC. Genes such as HLA-DQB1 [131], MCM2 [132], and MSH2 [133] were involved in pathogenesis of ACC. Metylation inactivation of tumor suppressor gene DNMT1 was responsible for progression of colon cancer [134], but loss of this gene may be associated with pathogen- esis of ACC. Genes such as MCM3 [135] and MCM6 [136] were associated with proliferation of different cancer cells such as ovarian cancer and lung cancer, but these genes may be liable for advancement of ACC. Genes such as COL1A1

Table 8 Target gene-miRNA interaction table
RegulationTFDegreeTarget geneRegulationTFDegreeTarget gene
UpTFDP167HSPA1ADownTFDP178F11R
UpEZH254PHOX2BDownGTF2E269CHAF1B
UpMAZ52H19DownKLF962FANCG
UpMXD451CEBPDDownELF161CENPF
UpKDM5B50DNAJC3DownZNF58061XRCC1
UpPHF850HOXA7DownMXD360IQGAP2
UpKLF950KCTD14DownSMAD560MAPKAPK5
UpSAP3050TIPARPDownIRF160RRM2
UpNR2F646HES1DownZNF2460ST6GALNAC2
UpSOX1345BZW1DownPHF859CHTF18
UpZNF58045LDLRDownKDM5B59NR3C1
UpHBP144DDCDownSAP3059TMPO
UpTGIF242GKDownSIN3A58HOXA13
UpXBP142TCF7DownCREB3L158PLA2G1B
UpMXD342XBP1DownATF157TP53INP1
UpZBTB3341HOXA9DownZNF7656C14orf80
UpSIN3A41HOXB2DownZBTB2656HCP5
UpZNF42340CNN3DownZBTB1155MAT1A
UpZNF2440GSTA4DownZFX54RAD54L
UpATF340MT1FDownNR2F654TYMS
UpCHD140YWHAZDownPOLR2A53CHAF1A
UpSSRP139NFIL3DownZNF50151BIRC5
UpZNF50138DLL1DownKLF1651FN1
UpRXRB38GABARAPL1DownMAZ50LAMA3
UpKLF1138HSPA5DownDMAP149BTBD11
UpSUZ1237TFAP2BDownZFP249DDR1
UpZNF7636CITED1DownTAF749HMMR
UpATF136CRLF1DownMBD147DEF6
UpIRF136IL6DownZNF32446DONSON
UpZBTB1136STAT3DownNR4A145CX3CR1
UpGATAD135MT1BDownNRF145NRF1
UpZBTB2635SELKDownETV445SULT2A1
UpCTBP235NOLC1DownZFP3744CABLES1
UpNRF134AK7DownFOXJ244CDCA5
UpETV434APOEDownCBFB44DEPDC7
UpHIC134CNN1DownSP144PRSS8
UpRAD2134EPB41L1DownELK144THOC3
UpZNF32434PAPSS2DownGABPA44ZNF302
UpKLF1634TMEM25DownKLF143LRIG3
UpYY133CTHDownZNF64443NUP107
UpHMG20B33NEDD9DownCHD143PHGDH
UpZFX33UNC5BDownPPARG43RACGAP1
UpIRF432CD83DownNCOR143TXNIP
UpFOXM132CYB561DownMXD441COL27A1
UpZNF34132DUSP5DownBCL641IDH2
UpBCL11A32EGR1DownKLF1141KIF22
UpELF132GDF15DownHDGF41LTB
UpMLLT132IPO7DownETS141MXD4
UpTHRB32PCK1DownMLLT140ADA
UpBCL11B32RAB34DownMYNN40BBC3
UpCEBPG32S100A9DownZFP6440BMF
Table 8 (continued)
RegulationTFDegreeTarget geneRegulationTFDegreeTarget gene
UpZBTB7A32TGFBR3DownWT140MCM3
UpZFP231DNERDownZBTB7A40RHOBTB3
UpKLF830FJX1DownNR2C240XYLT2
UpGATA430ID2DownMLX39DAND5
UpDMAP130LITAFDownZNF58939GMNN
UpZFP6430PTP4A1DownNFRKB39ZNF700
UpTFE330SCARB1DownZNF7138CCNE1
UpCTCF30SLC27A6DownHBP138CDH1
UpBCL629C7DownHMG20B38DPP4
UpZNF58929G0S2DownZNF238HOMER1
UpZNF7129PDK4DownGTF2F138KIAA0101
UpHMGN329TMOD1DownHMGN338NUDT1
UpMYNN28ALDH3A2DownDDX2038TTK
UpFOXA328ATP1B3DownFOSL137ANLN
UpRARA28BZW1DownREST37ANXA4
UpFOSL128CALD1DownARID4B37CABLES1
UpNR2C228CXCL2DownRERE37CDCA5
UpMLX28FOXK2DownRFXANK37HLA-DQB1
UpSP328GJA1DownTFE337LCN2
UpZNF61028PLATDownZNF19737NEK2
UpRCOR228SNAI1DownKDM5A37OIP5
UpSP227AS3MTDownSOX1337TAF1C
UpRERE27DHCR24DownZNF39436BARD1
UpREST27ECE2DownSSRP136FGG
UpMBD127EPB41L1DownZBTB4036MSH2
UpTRIM2827FGF9DownELF336NCOA6
UpZNF19727FUBP1DownTGIF236RFC4
UpDRAP127ICAM1DownHMG20A36SERPINA3
UpZFP3727MAT2ADownPOLR2H35CD69
UpSMAD427MT1EDownINSM235GADD45A
UpGLIS227SF1DownE2F435MAD2L1
UpGATA226CHGADownNR2F135PCYOX1L
UpZEB126SCG3DownKLF1335POLD1
UpHNF4G25C1SDownZBTB3335PPP1R13B
UpZNF225HOXA5DownID335SUCNR1
UpELF325HPDownZNF61035TIGD2
UpARID4B25IER3DownNFIL334GGH
UpGTF2F125JUNBDownNCOA134HIST1H2BH
UpZNF39425MAPK4DownNFYC34HIST1H4J
UpMYBL225MT1HDownRXRB34ITPKA
UpKLF725NPC1DownCREB134LAMB1
UpNFIA25PEG10DownCREM34UHRF1
UpMBD425RAMP1DownGLIS233APOBEC3A
UpINSM225SOCS3DownMEF2D33HIST1H1C
UpSOX525TESK1DownLEF133HIST1H2BE
UpTEAD325VASNDownADNP33HIST1H2BL
UpNFRKB24ANGPTL4DownWRNIP133HIST1H4F
UpZHX224AOC3DownETV133HIST1H4K
UpNCOR124HBBDownGATAD132CSRP2BP
UpPOLR2A24HEPHDownIKZF132CYP3A7
UpPPARG24MSI2DownGATA432HIST1H2BB
Table 8 (continued)
RegulationTFDegreeTarget geneRegulationTFDegreeTarget gene
UpL3MBTL224NPTX1DownZEB132HIST1H2BF
UpKDM1A24TLX2DownBCL11B32HIST1H2BI
UpGTF2E224G0S2DownKDM1A32HIST1H2BN
UpRFXANK23STAT3DownSP331AHR
UpCREB3L123CHSY1DownKLF631HIST1H2BC
UpTAF723RARRES2DownRCOR231HIST1H2BD
UpKLF122GNAZDownKLF831HIST1H4H
UpWT122NR2F1DownSUPT5H31MUC20
UpE2F522ANGPTL4DownZNF42331OSBPL6
UpSMARCA522PLATDownHIC131SMS
UpTFAP422SEMA3BDownL3MBTL231WNT5A
UpSMARCE122TPMTDownTHRB30CDCA7
UpGABPA22STARD6DownFOXM130FUK
UpNFYC22MAT2ADownEGR130HSPB1
UpBHLHE4022PDGFRADownBCL11A30KIF22
UpZNF10121CH25HDownCEBPG30MCM8
UpBCOR21SPON2DownMBD230MSH2
UpETS121MGAT2DownKLF730PCYOX1L
UpESRRA21CCL13DownCCNT230RALGDS
UpSP121AQP11DownESRRA30RFC5
UpWRNIP121SLC2A3DownIRF430ZG16B
UpDPF221SLC33A1DownZKSCAN130ZKSCAN1
UpELK121RAB34DownZNF10129ROR1
UpHDGF20SLC25A19DownBACH129ANKRA2
UpZNF64420PCK1DownMIXL129RHOBTB3
UpCREB120QPCTDownE2F529PAQR4
UpMBD220CREBL2DownSMARCA529SMARCA5
UpPOLR2H20PTX3DownGATAD2A29FGG
UpFOXJ220TIPARPDownZNF36629GPX8
UpZNF26319IRS1DownARNT29CD2
UpSMC319RND3DownZNF17529CCNB1
UpGATAD2A19GTPBP4DownBCOR29BBC3
UpPBX219CYP11A1DownSIRT628DDR1
UpHMG20A19FOSL2DownSMARCA428KIF22
UpPRDM1019CYP17A1DownTEAD328UBD
UpJUND19PTP4A1DownARID1B28PBK
UpEED19PDGFRADownGATA228POPDC2
UpZNF33518AASSDownTFAP428IDH2
UpZNF36618FUBP1DownNFIA28HIST1H2BO
UpGFI1B18CNN3DownSP227HIST1H2BL
UpSMARCA418KCTD14DownDRAP127MMP9
UpSIRT618EGR1DownSMARCE127PMAIP1
UpZKSCAN118C14orf132DownZNF63927BUB1
UpKLF618GSTA4DownGLI427ZBED3
UpID318CYB561DownZNF8327FUK
UpGLIS118CRLF1DownZNF1826CCNG2
UpMTA218SAA1DownSOX526EXO1
UpRNF217ADMDownATF326UGT1A6
UpSUPT5H17SDF2L1DownZNF58426CXCL9
UpZBTB4017MSI2DownZHX226MC1R
UpNR2F217RAMP1DownTBX2126GALNT10
Table 8 (continued)
RegulationTFDegreeTarget geneRegulationTFDegreeTarget gene
UpTHAP117IER3DownPML26MSH2
UpZNF38417PTP4A1DownZNF33525HIST1H2BN
UpSP717ID2DownGTF2A225CD69
UpMTA117HES1DownTHRAP325OIP5
UpNCOA117CEBPDDownJUNB25KIAA0922
UpPRDM117HOXA7DownCTCF24MMP9
UpTEAD117HSPA5DownRARA24ZNF266
UpKLF416DLL1DownHDAC124CCNB2
UpETV116SNAI1DownEZH224GPR150
UpLEF116RAB34DownTRIM2224NR3C1
UpADNP16RAB21DownSMAD424FBXO32
UpZNF17516ECHDC3DownYY123UGT1A6
UpATF416XBP1DownDPF223DNMT3B
UpZNF63916CTSDDownZNF55823RAI14
UpHCFC116JUNBDownCREB323HMBOX1
UpBACH116IL6DownHCFC123RANBP17
UpMIXL116GABARAPL1DownTEAD122FN1
UpMEF2D16CXCL2DownTSHZ122PBK
UpGTF2A216KCNK5DownUSF222NR3C1
UpZNF8316TIPARPDownSP722CHAF1A
UpCCNT216TLX2DownTRIM2422POLD1
UpHMBOX116HBBDownTBP22KIAA0101
UpGLI415CRLF1DownKLF421CDT1
UpMAX15MRASDownMTA221IGJ
UpKLF1315SDF2L1DownZNF12121DEF6
UpTRIM2215TRIM22DownZNF34121MYBL2
UpRELA15C1SDownRAD2121HOMER1
UpDDX2015ZBED1DownSIN3B21NUDT1
UpUSF215NR4A3DownZNF38421ENC1
UpEGR214ABRDownHES121F11R
UpZNF62314WFDC1DownEED20MICB
UpTSHZ114TGFBR3DownZNF26320GRIN2C
UpSIN3B14AOC3DownFOXA320PLK2
UpHDAC114YWHAZDownGMEB220CDCA7
UpTBX2114SELKDownSTAT120MCM2
UpCBFB14DNAJB9DownTRIM2820LAMB1
UpRFX114SYT13DownZNF38219BRD8
UpTCF714TNFRSF11BDownRNF219ANXA4
UpZNF58414UNC5BDownIRF219ANLN
UpCUX114PRKAR1ADownZNF20719MAPKAPK5
UpZNF1814FOXK2DownTARDBP19ZG16B
UpHHEX13AQP11DownATF418HIST1H2BE
UpTRIM2413SOAT1DownKAT2A18FANK1
UpMITF13GKDownEGR217EML1
UpNFE2L212NDRG1DownPRDM1017LRIG3
UpZNF55812NOLC1DownZNF51217CYP3A5
UpPKNOX112S100A8DownCDC5L17KCNK1
UpZNF12112ATP5LDownMXI117BIRC5
UpCREB312HSPA1ADownPOU2F217PMAIP1
UpARID1B12DUSP5DownHDAC616ADA
UpIKZF112SEMA3BDownHDAC216SLC2A4RG
Table 8 (continued)
RegulationTFDegreeTarget geneRegulationTFDegreeTarget gene
UpZNF51211ATP1B3DownTHAP116CDKN3
UpZNF711DDCDownNR2F216COL1A1
UpGMEB211SELKDownMBD416TP53INP1
UpZNF14311DNAJB9DownHNF4G16COL27A1
UpRAD5110ADRA2CDownPRDM116HOXA13
UpHDAC610ANGPTL4DownZNF62316ZNF404
UpZBTB110AKR1B1DownGFI1B16PRSS16
UpHDAC210IL1R2DownTCF716HIST1H4H
UpZBTB1710HOXA9DownGTF2B16CDCA5
UpRFX310ALDH3A2DownNFYB16FANCG
UpCTBP110HOXB2DownCUX116MMP9
UpCDC5L10CEBPBDownEBF115KLK1
UpZNF38210THBS1DownRELA15HIST1H2BE
UpSCRT110GSTT2DownPBX215HIST1H2BC
UpGATA310HSPA5DownGLIS115TIGD7
UpEBF19CD38DownNFIC15PMAIP1
UpKDM5A9SDF2L1DownZNF14314AHR
UpNFE29JUNBDownMTA114LCN2
UpARNT9LDLRDownCTBP214ST6GALNAC2
UpRCOR19AQP11DownZNF40714GALNT10
UpEP3009PI16DownCEBPA14DEPDC7
UpTARDBP9GSTA4DownSUZ1214HHEX
UpRUNX19GNAZDownNFE214RFC5
UpTAL19G0S2DownNFATC114HIST1H2BB
UpZNF2079TIPARPDownMTA314HIST1H4K
UpHDAC88SNAI1DownTAL113MUC20
UpTHRAP38HBBDownGATA113IQSEC1
UpSTAT18IKBKAPDownCEBPD13CLDN1
UpGTF2B8IER3DownFOXA213HIST1H2BD
UpMNT7VASNDownTEAD413SUCNR1
UpPML7RAB34DownBHLHE4013DMTF1
UpCEBPA7HSPA4LDownGATA312MAGED2
UpIRF27SDF2L1DownFOSL212CAP2
UpSREBF26AKR1B1DownRFX112DDR1
UpGATAD2B6EGR1DownZNF14612HIST1H4K
UpZNF4076CLDN5DownMYC12MTL5
UpTBP6MT1XDownCEBPB12HLA-DQB1
UpMYC6NR4A3DownRFX312DYRK2
UpNFATC16NDRG1DownSREBF212PRC1
UpGATA16CYB561DownFOXK211ZNF302
UpMTA36JUNBDownMAX11CCNB1
UpCBX86RPRMDownZNF711GADD45A
UpPTTG16IL6DownCHD711HIST1H2BO
UpPRDM25NPC1DownSCRT210FHOD1
UpZNF1465PEG10DownRCOR110PRSS16
UpSIX45SNAI1DownZNF20210PPP1R13L
UpATF25PLATDownATF210IGJ
UpEHMT25CRHDownIRF310HIST1H2BB
UpFOXA25PTGIRDownZBTB19XRCC1
UpTEAD45FOXK2DownJUND9PSAT1
UpDEK5ECE2DownMAFF9OIP5
Table 8 (continued)
RegulationTFDegreeTarget geneRegulationTFDegreeTarget gene
UpZNF2025PGM3DownEP3009PBK
UpZNF2175MGST1DownE2F69RRM2
UpMAFK5GNAZDownZNF5478FER1L4
UpPTRF5PRKAR2BDownMITF8HIST1H2BI
UpTEAD25RARRES2DownSCRT18NEK3
UpCHD44CREMDownZNF2178HSPB1
UpRXRA4APOC1DownDIDO18NUDT1
UpMXI14STAT3DownRUNX18PTCD1
UpZNF4884SOAT1DownJUN7HIST1H2BN
UpMYB4MAT2ADownPYGO27HIST1H2BE
UpDIDO14CXCL2DownMAFK7ZWINT
UpZNF164HOXA5DownMYB7KIF22
UpDNMT14SFPQDownTAF16HIST1H2BF
UpZHX14JUNBDownCTBP16LRIG3
UpSREBF14LDLRDownZNF2396RNFT2
UpPOU5F13FBLN1DownDEK6BMF
UpSCRT23ADAMTS1DownZBTB176HOMER1
UpZNF2643DNAJB9DownNFYA6CDCA8
UpJUN3CEBPBDownSMC36WNT5A
UpFOS3G0S2DownNFE2L26GADD45A
UpSPI13NEDD9DownZHX15ASPM
UpRUNX33DUSP5DownZNF6415DAND5
UpZNF5473KCNK5DownHLF5SERPINA3
UpE2F63FOXK2DownSETDB15ZNF404
UpPYGO23HSPA1ADownNFE2L15HIST1H1C
UpETV63GNAZDownMNT4APOBEC3A
UpTCF7L23SDF2L1DownZNF164ROR1
UpZNF6413GSTA4DownPOU5F14DNMT3B
UpCHD73PDGFRADownZNF2744ZNF443
UpPOU2F23TIPARPDownTBX34PLA2G1B
UpNONO3SOAT1DownRBBP54TIMELESS
UpZC3H11A2ADMDownSTAT34MCM8
UpUBTF2GSTA4DownPKNOX14HIST1H2BF
UpZNF2392SLC27A6DownZNF4883ITPKA
UpNFIC2CD83DownZNF585B3FBXO32
UpTSC22D42TSC22D4DownRUNX33GPR150
UpMCM32CLDN5DownSPI13IER5
UpSRF2EGR1DownFOS3BTBD11
UpELK42JUNBDownMAFG3HIST1H2BL
UpPOLR3A2GABARAPL1DownUBTF3DDB2
UpYBX12GNAZDownZC3H11A3C14orf80
UpSETDB12GTPBP4DownGATAD2B3KIF22
UpETS22HSPA1ADownPRDM23CCNE1
UpMAFF2PLA2G4ADownBCLAF13HIST1H2BJ
UpHLF2IGFBP6DownBDP13PRSS16
UpKAT2A2NR4A1DownGTF3C23HIST1H2BI
UpZFP411ADAMTS1DownBRF13HIST1H4H
UpMCM51GNAZDownPOLR3A3PRSS16
UpFOXA11GNAZDownETV63STK36
UpMCM71GNAZDownTEAD23RHOBTB3
UpCEBPZ1GNAZDownZNF1403ZNF700
Table 8 (continued)
RegulationTFDegreeTarget geneRegulationTFDegreeTarget gene
UpZNF1381HOXA5DownZFP412BBC3
UpPRDM121HOXA9DownZNF82POLD1
UpPPARGC1A1HSPA1ADownSIX42MUC20
UpHSF11HSPA1ADownSIX52ZNF133
UpUSF11ID2DownTCF7L22HIST1H2BD
UpHNF4A1IGFBP6DownBATF2FANK1
UpZNF81JUNBDownRXRA2FGG
UpBCL31NOLC1DownZNF2642GMNN
UpZZZ31NR2F1DownSREBF12MAPKAPK5
UpE2F41PDE8ADownSTAT5A2HIST1H2BB
UpAEBP21PEG10DownTCF32HIST1H1C
UpNANOG1PLEK2DownCEBPZ2KIAA0101
UpNR3C11PNMTDownTSC22D42TMEM191A
UpMAFG1PRKAR2BDownRFX52TP53INP1
UpCHD21RAB34DownCHD42KIF11
UpZMIZ11SDF2L1DownHNF4A2SLC2A4RG
UpSMAD21SDF2L1DownETS21BBC3
UpZNF585B1TLX2DownBCL31BBC3
DownMCM71BBC3
DownCHD21CDCA2
DownUSF11COL1A1
DownZNF354C1FABP3
DownFOXA11FANK1
DownTBL1XR11GADD45A
DownPRDM121HOXA13
DownPPARGC1A1HSPB1
DownHSF11HSPB1
DownYBX11LY6D
DownNONO1LY6D
DownEHMT21NPTX2
DownCBX81PRSS16
DownHDAC81PSAT1
DownZNF1381ZNF302

Degree-no of target gene interact with TF. We taken any one target gene in table TF transcription factors

[137], COL3A1 [138], LAMA3 [139], and LAMB1 [140] were linked with invasion of different cancer cells such as gastric cancer, bladder cancer, head and neck cancers, and colorectal cancer, but these genes may be diagnosed with growth of ACC. Mutation in genes such as EXO1 [141] and POLD1 [142] were associated with pathogenesis of colo- rectal cancer, but alteration in this gene may be identified with growth of ACC. SNP in LIG1 was involved in progres- sion of lung cancer [143], but this gene may be responsi- ble for development of ACC. HIST1H2BB, HIST1H2BC, HIST1H2BD, HIST1H2BE, HIST1H2BF, HIST1H2BH, HIST1H2BI, HIST1H2BJ, HIST1H2BL, HIST1H2BN, HIST1H2BO, HIST1H4F, HIST1H4H, HIST1H4J, HIST1H4K, HLA-DRB4, MAT1A, COL14A1, COL27A1,

COL4A5, COL5A2, RFC4, and RFC5 were novel biomark- ers for pathogenesis of ACC in these pathways.

In GO enrichment analysis, up regulated genes were mainly associated with all GO categories (BP, CC and MF) such as blood vessel morphogenesis, extracellular matrix, and heparin binding. Genes such as adrenomedullin (ADM) [144], apolipoprotein E (APOE) [145], GATA6 [146], and RARRES2 [147] were responsible for pathogenesis of ACC. Genes such as CDH2 [148], CITED1 [149], FZD4 [150], STARD13 [151], XBP1 [152], and latexin (LXN) [153] were associated with invasion of different cancer cells such as lung cancer, colorectal cancer, prostate cancer, breast can- cer, and thyroid cancer, but these genes may be liable for invasion of ACC cells. Methylation inactivation of tumor

Fig. 14 TF-gene network of predicted target up regulated genes. Pink triangles are TFs and green circles are target upregulated genes. Yellow lines means interaction with adjutant genes or TFs
Fig. 15 TF-gene network of predicted target down-regulated genes. Blue triangles are TFs and pink circles are target down-regulated genes. Yellow lines means interaction with adjutant genes or TFs

suppressor genes such as DLL1 [154], HAND2 [155], and UNC5B [156] were identified with progression of different cancer such as lung cancer endometrial cancer and colorectal cancer, but loss of these genes may be involved in develop- ment of ACC. High expression of genes such as ENPP2 [157], GJA1 [158], HES1 [159], RAMP1 [160], SIRT1 [161], TFAP2B [162], TNFRSF11B [163], and SAA1 [164] were important for advancement of different cancer such as hepatocellular carcinoma, endometrial cancer, colon can- cer, prostate cancer, lung cancer, and gastric cancer, but elevated expression of these genes may be diagnosed with ACC. Genes such as HOXA5 [165] and HOXA7 [166] were linked with cell cycle progression in different cancer such as breast cancer and ovarian cancer, but these genes may be involved in cell cycle progression in ACC. SNP in NRXN3 was important for development of breast cancer [167], but this polymorphic gene may be involved in development of ACC. Low expression of TGFBR3 was responsible for advancement of prostate cancer [168], but loss of this gene may associated with growth of ACC. Platelet-derived growth factor receptor, alpha polypeptide (PDGFRA), SCG2, TCDD-inducible poly(ADP-ribose) polymerase (TIPARP),

Fig. 16 Kaplan-Meier survival curves using TCGA data validate the prognostic value of genes expressed in ACC. (Blue is low expression and Red is high expression)

A YWHAZ

B STAT1

C ICAM1

D SH3BP5

E CD83

Effect of YWHAZ expression level on AGG patient survival

Effect of STATE expression level on ACG patient survival

Effect of ICAMi expression lovell on ACC patent survival

-

Effect of SH36P5 expression level on ACG pašent survival

Efect of COBS expression level on ACC patient survival

D=0.012

D=0.024

p= 0.008

p= 0.016

p = 0.00016

-

F FN1

G TK1

H HIST1H1C

I CABLES1

J MCM3

ETeil of FNE espressien level en ACC patient survival

Ellest of HISTIHIC expression level on ACC patient survival

Effect of CABLES1 expression level on ACC patient survival

te

Effect of Mcats espressien level en ACC patient survival

Effect of THE expression level on ACC patient survival

·

-

-

p = 0.0009

P=0.017

p= 0.00011

P=0.0001

-

-

-

-

Fig. 17 Validation of the expression of hub genes in the TCGA database. High expression of hub genes in stages 4. ACC:Adrenocortical carci- noma

YWHAZ

STAT1

ICAM1

CD83

Expression of YWHAZ in ACC based on individual cancer stages

Expression of STAT1 in ACC based on individual cancer stages

Expression of ICAM1 in ACC based on individual cancer stages

Expression of CD83 in ACC based on individual cancer stages

600

100

40

125

500-

80

30

100

Transcript per million

Transcript per million

Transcript per million

Transcript per million

400

60

75

20

300

40

50

10

200-

20

25

1

100

0

L

0

0

Stageż (n=37)

Stage’s (n=16)

Stage4

-20

Stageż (n=37)

Stage 3 (n=16)

Stage4 I == 151

-10

Stage1

Stage2 (n=37)

Stage3 (n=16)

Stage4 (n=15)

-25

Stage 1

Stage2

Stapel

Stage2 (n=37)

Stapel

(n=16)

Stage4

TCGA samples

TCGA samples

TCGA samples

TCGA samples

FN1

TK1

HIST1H1C

MCM3

Expression of FN1 in ACC based on individual cancer stages

Expression of TK1 in ACC based on individual cancer stages

Expression of HIST 1H1C in ACC based on individual cancer stages

Expression of MCM3 in ACC based on individual cancer stages

300

125

250-

150

250

100

200

125

Transcript per million

200

Transcript per million

75

Transcript per million

150

Transcript per million

100

150

50

75

100

1:00

50

25

50

50

25-

-

0

-

-

L

-

0-

-

1

0

50

-25

50

Stage 1

Stagez

Stage3

Stage4 (n=15)

Stage 1

Stageż (n=37)

Stage3 (n=16)

Stage4 It=15)

Stage1

Stage2 (n=37)

Stage1 (n-36)

Stage4 (n=15)

-25

Stage1 (n=9)

Stage2 (n=37)

Stage3

Stage4 (n=15)

TCGA samples

TCGA samples

TCGA samples

TCGA samples

and IL1RL1 were novel biomarkers for pathogenesis of ACC in these GO categories. Meanwhile, down regulated genes were mainly associated with all GO categories such as cell cycle phase transition, chromosome, centromeric region, and protein dimerization activity. High expression of genes such as anillin, actin binding protein (ANLN) [169], NEK2 [170], timeless homolog (TIMELESS) [171], TPX2 [172], TTK protein kinase (TTK) [173], CDCA8 [174], KIF18A [175], OIP5 [176], SPC25 [177], ZWINT [178], asparagine synthetase (ASNS) [179], E2F8 [180], LCN2 [181], and RAB11FIP4 [182] were important for progression of dif- ferent cancers such as pancreatic cancer, breast cancer, lung cancer, colorectal cancer, gastric cancer, ovarian cancer, and hepatocellular carcinoma, but increased expression of these

genes may be associated with development of ACC. Genes such as BIRC5 [183], BUB1 [184], CCNB1 [185], CCNB2 [186], CDCA5 [187], CDKN3 [188], centromere protein F (CENPF) [189], and SPAG5 [190] were associated with proliferation of different cancer cells such as breast cancer, gastric cancer, hepatocellular carcinoma, and ovarian cancer, but these genes may be linked with proliferation of ACC cells. Methylation inactivation of tumor suppressor genes such as CABLES1 [191], GADD45A [192], PLK2 [193], and NR3C1 [194] were involved in pathogenesis of different cancers such as ovarian cancer, breast cancer, and colorectal cancer, but loss these genes may be identified with develop- ment of ACC. SNP in genes such as hyaluronan-mediated motility receptor (HMMR) [195]. DNMT3B [196], aryl

Fig. 18 Validation of the expression of hub genes in the TCGA database. High expression of hub genes in stages 2 and 1. ACC:Adrenocortical carcinoma

SH3BP5

CABLES1

Expression of SH3BP5 in ACC based on individual cancer stages

Expression of CABLES1 in ACC based on individual cancer stages

400

15

12.5

300

Transcript per million

Transcript per million

10

200

7.5

100

5

2.5

0

0

-100

-2.5

Stage1 (n=9)

Stage2 (n=37)

Stage3 (n=16)

Stage4 (n=15)

Stage1 (n=9)

Stage2 (n=37)

Stage3 (n=16)

Stage4 (n=15)

TCGA samples

TCGA samples

YWHAZ

0%

STAT1

0%

ICAM1

3%

SH3BP5

0%

CD83

1.1%

FN1

1.1%

TK1

0%

HIST1H1C

0%

CABLES1

1.1%

MCM3

1.1%

Fig. 19 Genetical alteration analysis (genetical alterations towards these ten genes)

Genetic Alteration

Missense Mutation (unknown significance)

Amplification

No alterations

YWHAZ

STAT1

ICAM1

SH3BP5

CD83

FN1

TK1

HIST1H1C

CABLES1

MCM3

Expression Heatmap

-3

3

No data

hydrocarbon receptor (AHR) [197] hydroxyprostaglandin dehydrogenase 15-(NAD) (HPGD) [198], and UGT1A6 [199] were liable for advancement of different cancer such as breast cancer, lung cancer, and colorectal cancer, but these polymorphic genes may be linked with development of ACC. Alteration in genes such as MAD2L1 [200] and BARD1 [201] were associated with pathogenesis of breast cancer, but mutation in this gene may be involved in devel- opment of ACC. Genes such as maternal embryonic leucine zipper kinase (MELK) [202], RRM2 [203], NR0B1 [204], and TOP2A [14] were important for pathogenesis of ACC. Alteration in tumor suppressor gene PLAGL1 was liable for growth of pheochromocytomas [205], but mutation in this gene may be associated with pathogenesis of ACC. CEP192, KNTC1, MCM8, KIF22, NUP107, STAG3, BTBD11, CD2, CD3D, DPP4, fibroblast activation protein, alpha (FAP) granzyme A (granzyme 1, cytotoxic T-lymphocyte-associ- ated serine esterase 3) (GZMA), H2BFS, hematopoietically expressed homeobox (HHEX), HOMER1, v-kit Hardy- Zuckerman 4 feline sarcoma viral oncogene homolog (KIT), NCOA6, SRGAP2, and TCFL5 were novel biomarkers for pathogenesis of ACC in these GO categories.

In this study, we finally identify five hub genes (up regu- lated) were in PPI network with high node degree such as YWHAZ, HSPA5, STAT3, APOE, and GRK5. High expres- sion of tyrosine 3-monooxygenase/tryptophan 5-monooxy- genase activation protein, zeta polypeptide (YWHAZ) was responsible for progression of head and neck cancer [206], but elevated expression of this gene may be identified with growth of ACC. Genes such as HSPA5 [207] and GRK5 [208] were associated with invasion of different cancer cells such as colorectal cancer and prostate cancer, but these genes may be liable for invasion of ACC cells. Five hub genes (up regulated) were in PPI network with high betweenness such as YWHAZ, HSPA5, STAT3, TH, and CD83. SNP in CD83 was diagnosed with growth of cervical cancer [209], but this polymorphic gene may be involved in development of ACC. Five hub genes (up regulated) were in PPI network with high stress such as YWHAZ, HSPA5, ICAM1, HOXB2, and STAT3. ICAM1 was linked with invasion of breast cancer cells [210], but this gene may be associated with invasion of ACC cells. High expression of HOXB2 was involved in pathogenesis of cervical cancer [211], but elevated expres- sion of this gene may be responsible for progression of ACC. Five hub genes (up regulated) were in PPI network with high closeness such as YWHAZ, HSPA5, NR4A1, IRS1, and MAP3K5. MAP3K5 was important for invasion of prostate cancer cells [212], but this gene may be linked with invasion of ACC cells. Five hub genes (up regulated) were in PPI network with low clustering coefficient such as CRLF1, CRH, ARHGAP18, FJX1, and FMO3. Corticotro- pin releasing hormone (CRH) was liable for progression of pheochromocytomas [213], but this gene may be associated

with advancement of ACC. ARHGAP18 was identified with invasion of breast cancer cells [214], but this gene may be involved in invasion of ACC cells. High expression of FJX1 was diagnosed with growth of nasopharyngeal carcinoma [215], but over expression of this gene may be identified with progression of ACC. SNP in FMO3 was responsible for advancement of colorectal cancer [216], but this poly- morphic gene may be associated with development of ACC. Meanwhile, five hub genes (down regulated) were in PPI network with high node degree such as FN1, VCAM1, UBD, BARD1, and TK1. High expression of genes such as VCAM1 [217] and ubiquitin D (UBD) [218] were respon- sible for pathogenesis of different cancers such as gastric cancer and colon cancer, but elevated expression of these genes may be liable for growth of ACC. Five hub genes (down regulated) were in PPI network with high between- ness such as FN1, UBD, VCAM1, BARD1, and TK1. Five hub genes (down regulated) were in PPI network with high stress such as FN1, UBD, VCAM1, SLPI, and BARD1. Secretary leukocyte protease inhibitor (SLPI) was linked with invasion of ovarian cancer cells [219], but this gene may be involved in invasion of ACC cells. Five hub genes (down regulated) were in PPI network with high closeness such as FN1, VCAM1, MCM3, PHGDH, and MCM6. High expression phosphoglycerate dehydrogenase (PHGDH) was responsible for pathogenesis of melanoma [220], but over expression of this gene may be identified with growth of ACC. Five hub genes (down regulated) were in PPI network with low clustering coefficient such as CYP3A5, POPDC2, PNLIPRP2, KIAA1407, and CX3CR1. SNP in CYP3A5 was important for pathogenesis of breast cancer [221], but this polymorphic gene may associated with development of ACC. CX3CR1 was linked with invasion of prostate can- cer cells [222], but this gene may be involved in invasion of ACC cells. POPDC2, PNLIPRP2, and KIAA1407 were novel biomarkers for pathogenesis of ACC in these PPI network.

Hub genes (up regulated) such as YWHAZ, GRK5, NOLC1, ID2, STAT3, HES1, NR4A1, ZNF331, APOE, PLAT, C1S, SERPING1, HP, APOC1, SH3BP5, STAT1, IPO7, and HSPA4L were in all four modules. NOLC1 was associated with proliferation of hepatocellular carcinoma cell [223], but this gene may be responsible for progres- sion of ACC cells. High expression of genes such as ID2 [224], APOC1 [225], and HSPA4L [226] were involved in pathogenesis of different cancer such as pancreatic cancer, lung cancer, and hepatocellular carcinoma, but increase expression these genes may be linked with growth of ACC. Methylation inactivation of tumor suppressor gene ZNF331 was important for development of colorectal cancer [227], but loss of this gene may be liable for growth of ACC. SNP in haptoglobin (HP) was associated with pathogenesis of breast cancer [228], but this polymorphic gene may be liable

for growth of ACC. IPO7 was involved in proliferation of prostate cancer cells [229], but this gene may be associ- ated with proliferation of ACC cells. C1S and SH3BP5 were novel biomarkers for pathogenesis of ACC in these modules. Meanwhile, hub genes (down regulated) such as VCAM1, FN1, MCM3, MCM2, MCM6, UBD, MAGED2, HIST1H1C, MAD2L1, PHGDH, HSPB1, HIST1H2BJ, UHRF1, NCOR2, TOP2A, PBK, ASNS, TMPO, HMGB2, HIST1H2BL, TYMS, CHAF1B, CCNE1, POLD1, CDT1, and PRC1 were in all four modules. Methylation inactiva- tion of tumor suppressor gene HSPB1 was responsible for progression of prostate cancer [230], but loss of this gene may be identified with pathogenesis of ACC. High expres- sion of genes such as UHRF1 [231] and PDZ binding kinase (PBK) [232] were important for advancement of different cancer such as lung cancer and prostate cancer, but elevated expression of these genes may be associated with develop- ment of ACC. NCOR2 was responsible for proliferation of glioblastoma cells [233], but this gene may be linked with proliferation of ACC cells. MAGED2 HIST1H1C, thymo- poietin (TMPO), CHAF1B, and PRC1 were novel biomark- ers for pathogenesis of ACC in these modules.

Target genes (up regulated) such as YWHAZ, GATA6, LDLR, BZW1, and IGFBP5 were in target genes-miRNA regulatory network. BZW1 was novel biomarker for patho- genesis of ACC in this network. Meanwhile, target genes (down regulated) such as TXNIP, MAPKAPK5, PMAIP1, RAD51, and MICA were in target genes-miRNA regula- tory network. Decrease expression of tumor suppressor genes such as thioredoxin interacting protein (TXNIP) [234] and PMAIP1 [235] was diagnosed with growth of different cancer types such as thyroid cancer and pancreatic cancer, but loss of expression of these genes may liable for patho- genesis of ACC. High expression of RAD51 was involved in pathogenesis of breast cancer [236], but elevated expres- sion of this gene may be linked with growth of ACC. MAP- KAPK5 and MHC class I polypeptide-related sequence A (MICA) were novel biomarkers for pathogenesis of ACC in this network.

Target genes (up regulated) such as HSPA1A, PHOX2B, H19, CEBPD, and DNAJC3 were in target genes-TF regu- latory network. HSPA1A was associated with pathogenesis of colorectal cancer [237], but this gene may be important for development of ACC. Inactivation of H19 was involved in pathogenesis of ACC [238]. PHOX2B and DNAJC3 were novel biomarkers for pathogenesis of ACC in this network. Meanwhile, target genes (down regulated) such as F11R, CHAF1B, FANCG, CENPF, and XRCC1 were in target genes-TF regulatory network. F11R was linked with advancement of glioma [239], but this gene may be associated with development of ACC. SNP in genes such as fanconianemia, complementation group G (FANCG) [240], and XRCC1 [241] were liable for progression of different

cancers such as pancreatic cancer and breast cancer, but these genes may be liable for growth of ACC.

Survival analysis revealed that genes such as YWHAZ, STAT1, ICAM1, SH3BP5, CD83, FN1, TK1, HIST1H1C, CABLES1, and MCM3 were predicting shorter survival of ACC. Expression levels revealed that hub genes such as STAT1, ICAM1, CD83, FN1, TK1, HIST1H1C, and MCM3 were highly expressed in ACC (stages 4), meanwhile those such as SH3BP5 and CABLES1 were highly expressed in ACC (stage 2 and stage 1).

In conclusion, we diagnosed several hub genes and path- ways that were closely related to the initiation and progres- sion of ACC using a series of bioinformatics analyses of DEGs in cancer and normal samples. Identification of the associated genes, YWHAZ, FN1, GRK5, VCAM1, GATA6, TXNIP, HSPA1A, and F11R, provided greater insight into the specific molecular mechanisms underlying ACC occur- rence and development, especially in terms of the path- ways involved in catecholamine biosynthesis, aldosterone synthesis and secretion, pyrimidine deoxyribonucleosides salvage, and systemic lupus erythematosus. Upon further experimental validation of these results, these genes may serve as potential research targets for therapy and thereby contribute to greater understanding of the molecular mecha- nisms underlying the progression of ACC.

Acknowledgements I thank Demeure, Arizona State University, 1001 S. McAllister Ave, Tempe, AZ, USA very much, the author who depos- ited their microarray dataset, GSE19775, into the public GEO database.

Author contributions Ali Mohamed Alshabi associated with project administration, methodology, and review and editing; Ali Mohamed Alshabi, Ibrahim Ahmed Shaikh, and Basavaraj Vastrad participated in writing original draft and investigation; and Chanabasayya Vastrad performed software, supervision, formal analysis, and validation. Basa- varaj Vastrad and Ali Mohamed Alshabi made substantial contributions to acquisition of resources, formal analysis, and validation.

Availability of data and materials The datasets supporting the conclu- sions of this article are available in the GEO (Gene Expression Omni- bus) (https://www.ncbi.nlm.nih.gov/geo/) repository. [(GSE19775) (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc= GSE19775)].

Compliance with ethical standards

Conflict of interest The authors declare that they have no conflicts of interest.

Ethical approval This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent No informed consent because this study does not contain any human or animal participants.

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