ANO1 expression is associated with male survival in lung squamous cell carcinoma

Abstract

Lung cancer is the leading cause of cancer deaths, with lung squamous cell carcinoma (LUSC) accounting for a substantial proportion of cases. LUSC exhibits significant variability in patient outcomes, influenced by clinicopathological factors such as stage, age, and sex, with men exhibiting higher rates of incidence and poorer outcomes compared to women. Therefore, prognosis modeling and customized approaches to LUSC therapy require the characterization of the biological mechanisms that differentiate tumors and patient outcomes across sexes. Using data from The Cancer Genome Atlas (TCGA), this study characterized gene expression patterns that distinguish male and female LUSC. Specifically, differential expression, survival, and Cox regression analyses assessed the prognostic value of ANO1 (Anoctamin 1) expression and methylation in LUSC. Analyses uncovered a significant overexpression of ANO1 in a subset of male LUSC tumors compared to a much lower expression in normal lung and female LUSC tumors. High ANO1 expression was associated with poor survival outcomes in male subjects. High ANO1 gene body methylation mirrored gene expression and was similarly associated with poor survival outcomes. ANO1’s prognostic value remained significant in a multivariate Cox regression analysis, establishing it as an independent prognostic biomarker. ANO1’s marked sex-specific differences in expression and prognostic value indicate its role in the sex disparity of LUSC survival, highlighting its potential as a biomarker and a target for sex-specific customized therapies.