Work

Development and external validation of a psychological stress-related gene signature for overall survival prediction in bladder cancer

Year: 2026

Type: article

Abstract: Background: Psychological stress may influence tumor progression through neuroendocrine, inflammatory, immune, and microenvironmental mechanisms, but its prognostic relevance in bladder cancer (BLCA) remains incompletely defined. We aimed to develop and externally validate a psychological stress-related gene (PRG) signature for overall survival (OS) and characterize its biological context. Methods: This retrospective study used The Cancer Genome Atlas bladder cancer cohort (TCGA-BLCA; n=404, 176 deaths) for development and Gene Expression Omnibus (GEO) GSE48075/GSE48277 (n=73, 45 deaths) for external validation. Candidate PRGs underwent differential-expression analysis, univariate Cox screening, and least absolute shrinkage and selection operator (LASSO)-Cox modeling. The fixed 23-gene model was evaluated by survival and prognostic-performance analyses. Post hoc analyses assessed functional annotation, clinicopathological subgroups, stress-related pathway scores, immune functional-state and Tumor Immune Dysfunction and Exclusion (TIDE) features, drug-pathway associations, and network-defined hub genes. Results: were the top network hubs; all were prognostic in TCGA after correction, whereas GEO estimates were directionally concordant but not significant after correction. Conclusions: The fixed PRG signature provided research-level prognostic stratification and was associated with stress-related inflammatory, immune, and tumor-microenvironment programs in BLCA. Because external discrimination was modest and the post hoc biological analyses were exploratory, independent prospective and experimental validation is required before clinical use.

Source: Translational Andrology and Urology

DOI: 10.21037/tau-2026-0679