Pan-Cancer Analysis of a Depression-Related Gene Signature Identifies an Immunosuppressive Tumor Microenvironment and Links to Immunotherapy Response in Breast Cancer

Abstract Background: Depression has been increasingly associated with cancer progression and patient outcomes, yet its molecular and immunological correlates within tumors remain incompletely understood. This study aimed to investigate depression-associated gene signature across cancers and evaluate their relationship with tumor biology, immune microenvironment, and clinical outcomes, with a focus on breast cancer. Methods: A depression-related gene signature comprising 382 genes was obtained from the Molecular Signatures Database and used to compute a DScore via single-sample gene set enrichment analysis (ssGSEA)