Pan-cancer landscape of APEX1 expression and genomic alterations: Associations with clinical outcomes and functional validation in lung cancer.

Abstract

This pan-cancer study systematically evaluated APEX1 expression, genomic alteration status, and prognostic value across 13,270 tumors and 2544 normal tissues from TCGA and GTEx. APEX1 overexpression was prominent in bladder, breast, and colon adenocarcinomas and correlated with advanced tumor stages and survival outcomes in a cancer-type-specific manner, with unfavorable associations in selected tumor contexts and an opposite favorable association in KIRC. Low-frequency APEX1 genomic alterations require cautious interpretation and may be associated with adverse outcomes in selected tumor contexts. Statistical methods including t-tests, ANOVA, Cox regression, Benjamini-Hochberg false-discovery rate correction for cohort-wise OS analyses, and log-rank tests were used to correlate APEX1 expression or alteration status with survival outcomes. The findings suggest that APEX1 expression and low-frequency genomic alterations are associated with tumor progression and worse patient outcomes in selected cancer contexts. This study supports APEX1 as a candidate prognostic indicator requiring further validation and suggests its potential value for future clinical stratification research. The pan-cancer approach improves contextual breadth, and the large sample size adds robustness. The observed relevance of APEX1 across malignancies supports further evaluation of its value for risk stratification and treatment planning. Future prospective studies are needed to validate its clinical utility. This work contributes to the growing field of DNA repair-related biomarkers and may inform future studies of APEX1-targeted therapeutic strategies.