ELSEVIER
Surgery
journal homepage: www.elsevier.com/locate/surg
SURGERY
MOWEMBER 2018
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Letter to the editor on “Identifying genomic signatures of recurrence in adrenocortical carcinoma after R0 resection”
To the Editor:
We recently read with great interest the study by Greenspun et al1 that analyzed data from 92 patients with adrenocortical carci- noma (ACC) from The Cancer Genome Atlas (TCGA), including 84 pa- tients with recurrence data. The findings indicated a recurrence rate of 52% among ACC patients and 40.3% in those who underwent R0 resection. Patients with recurrence showed significantly increased variants in the WNT, PI3K, and cell cycle pathways (P <. 05), whereas MYC pathway alterations were significantly associated with early recurrence (P =. 0339). These results suggest that genetic alterations in the WNT, PI3K, and cell cycle pathways may serve as independent predictors of ACC recurrence and have potential clinical utility. How- ever, there are several issues that merit further exploration to enhance the interpretation and applicability of these findings.
First, multiple testing correction is essential for ensuring meth- odologic rigor in genomic studies. Given that multiple pathways were analyzed in this study, the risk of false positives inherently in- creases without proper adjustments. It was not explicitly mentioned whether corrections for multiple testing were applied. The lack of such adjustments could lead to significant results that may be spurious rather than reflective of true biological relationships. There- fore, we recommend that the authors provide details regarding mul- tiple testing corrections and report both unadjusted and adjusted P values to ensure the robustness and rigor of the findings.
Second, the origin of patients significantly impacts the generaliz- ability of genomic findings. Differences in genomic characteristics, lifestyles, environmental exposures, and health care availability across regions and ethnicities can influence ACC biology and the fre- quency of genetic alterations. As TCGA primarily includes patients from the United States, these results may not fully capture the diver- sity of the global population. Although the authors acknowledged the rarity of ACC and the challenges of sample collection, future studies should consider incorporating multicenter, geographically diverse data sets to reduce potential bias and improve the applica- bility of the findings across different populations.
Finally, the potential therapeutic implications of the identified cancer-related pathways warrant further discussion. Variants in pathways such as WNT, PI3K, and cell cycle have been extensively studied in other malignancies and demonstrated potential as tar- gets for targeted therapies.2,3 However, this study did not elaborate on the feasibility of leveraging these pathways for ACC treatment. We encourage the authors to explore whether these genetic alter- ations could serve as targets for developing personalized therapies for ACC and evaluate their potential within the context of existing clinical trial data on targeted or combination therapies.
In conclusion, although the above considerations warrant further research, this study offers valuable insights into the
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genomic landscape of ACC recurrence and its underlying molecular mechanisms. Future research should aim to expand sample sizes, integrate multicenter and diverse data sets, and assess the thera- peutic applicability of these genomic alterations. Such efforts will enhance the precision of ACC recurrence risk assessment and lay the groundwork for the development of personalized treatment strategies to improve patient outcomes.
Funding/Support
This study received funding from the National Natural Science Foundation of China (82,303,086).
Conflict of Interest/Disclosures
This article has no conflicts of interest.
CRediT authorship contribution statement
Mingwei Zhan: Writing - original draft, Writing - review & editing. Zheng Tang: Writing - review & editing. Xu Fu: Conceptu- alization, Writing - original draft, Writing - review & editing.
References
1. Greenspun BC, Chirko D, Toor R, et al. Identifying genomic signatures of recurrence in adrenocortical carcinoma after R0 resection. Surgery. 2025;178: 108886.
2. Fruman DA, Chiu H, Hopkins BD, Bagrodia S, Cantley LC, Abraham RT. The PI3K pathway in human disease. Cell. 2017; 170:605-635.
3. Finn RS, Crown JP, Lang I, et al. The cyclin-dependent kinase 4/6 inhibitor palbo- ciclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PAL- OMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol. 2015;16:25-35.
Mingwei Zhan, MD Department of Urology, Jinling Hospital Affiliated Hospital of Medical School, Nanjing University Nanjing, China
Zheng Tang, MD The Affiliated Suzhou Hospital of Nanjing Medical University Suzhou Municipal Hospital, Gusu School Suzhou, Jiangsu, China
Xu Fu, MD* The Affiliated Suzhou Hospital of Nanjing Medical University Suzhou Municipal Hospital, Gusu School Suzhou, Jiangsu, China
“Corresponding author.
E-mail address: xufu0306@foxmail.com (X. Fu).
Accepted 10 November 2024