AKR1B1: a prognostic biomarker linking oxidative stress to apoptosis in adrenocortical carcinoma.

BACKGROUND

Adrenocortical carcinoma (ACC) is a rare and highly aggressive malignancy with a poor prognosis. Oxidative stress, known to contribute to tumor progression, is believed to play a significant yet poorly understood role in ACC pathogenesis. The aims of this study were to construct a robust prognostic risk model for ACC based on oxidative stress-related genes and to experimentally investigate the functional impact of a key identified gene on oxidative stress and apoptosis.

METHODS

Using RNA sequencing data and clinical information from The Cancer Genome Atlas (TCGA) ACC cohort, GSE75415 and GSE33371, we identified and validated the prognostic oxidative stress-related risk signature. The risk model's predictive accuracy was assessed using Kaplan-Meier and ROC curve analyses. The tumor microenvironment and immune responses was performed by xCell and tumor immune dysfunction and exclusion (TIDE). Furthermore, in vitro experiments, including western blot, acridine orange/ethidium bromide (AO/EB) and oxidative stress index detection assays, were conducted to explore the roles of the pivotal gene, AKR1B1, in regulating apoptosis and oxidative stress.

RESULTS

We developed and validated a novel oxidative stress-related gene signature that effectively stratified ACC patients into high- and low-risk groups. The low-risk patients had better clinical overall survival and were predicted to have increased sensitivity to immunotherapy. Functional studies demonstrated that overexpression of AKR1B1 significantly alleviated H2O2-induced apoptosis and enhanced cellular antioxidant capacity.

CONCLUSION

Our findings underscore the important functional role of AKR1B1 in inhibiting oxidative stress and apoptosis in ACC, highlighting it as a potential therapeutic target in ACC.