Anila Hashmi^1,2,3, Stan Sidhu^3,4, Gyorgy Hutvagner²

¹NSW Health Pathology, Liverpool, NSW, Australia;² University of Technology Sydney, Sydney, NSW, Australia; ³ Kolling Research Institute, NSW Health, Sydney, NSW, Australia; Endocrine Surgery Unit, Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, NSW, Australia

Background: Adrenocortical carcinoma (ACC) is an aggressive malignancy with high recurrence rate, even after complete surgical resection. Currently biomarkers are limited in their ability to assist diagnosis or prognostication¹. While secretion of cortisol and androgens is associated with poorer outcomes², biomarkers with greater prognostic accuracy would be desirable. AGO2, a key regulator of miRNA function, plays a significant role in tumour biology³. This study evaluated AGO2’s prognostic potential in ACC by correlating its expression with clinicopathological features, including hormone status, and overall survival.

Methods: Clinicopathological parameters, including age, sex, Weiss score, pathological stage, molecular subtype, hormone production, and overall survival, were analysed for associations with AGO2 gene expression (TCGA-79-ACC) and protein levels (Kolling Tumour bank-15- ACC)³.  P-values <0.05 were considered significant.

Results: Elevated AGO2 expression was significantly associated with poor survival (p <0.001), high Weiss scores, and advanced tumour stage. Notably, increased AGO2 expression was linked with poor outcomes after controlling for hormone status.

Conclusion: AGO2 shows potential as an ACC biomarker, offering independent prognostic information. These findings support the value of further investigation into the role AGO2 could play in supporting the diagnosis and prognosis of ACC.

Statement of Originality: This study is the first to evaluate AGO2 expression in relation to clinicopathological factors, including hormone status, in ACC, providing original analyses into AGO2’s potential role as a prognostic biomarker in this malignancy.

References: 

1) Fassnacht, M., et al. (2018). ESE Clinical Practice Guidelines on adrenocortical carcinoma. Eur J Endocrinol, 179(4), G1–G46. https://doi.org/10.1530/EJE-18-0608

2) Nastos, C., et al. (2024). Hormone-secreting ACC and survival: A meta-analysis. Langenbecks Arch Surg, 409(1), 316. https://doi.org/10.1007/s00423-024-03507-5

3) Hashmi, A., et al. (2024). AGO2 as a biomarker in adrenocortical carcinoma. Endocr Relat Cancer. https://doi.org/10.1530/ERC-24-0061