Identification of a 9-gene autophagy-related signature for predicting prognosis and immune exhaustion features in breast cancer.

[UNLABELLED] To address the prognostic limitations in breast cancer (BRCA), we integrated transcriptomic profiles from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) to construct a novel 9-gene autophagy-related signature via Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression. The model demonstrated robust predictive accuracy for overall survival in the training cohort (HR = 2.28,  0.001) and maintained stability in external validation (AUC = 0.740). Mechanistically, the risk score was significantly associated with selective autophagy pathways and an immune-exhausted microenvironment characterized by T-cell dysfunction. Furthermore, drug sensitivity profiling identified a positive correlation between the risk gene MTDH and sensitivity to Vincristine and Gemcitabine. This study presents a reliable risk-stratification tool that bridges autophagic mechanisms with personalized chemotherapy guidance.

[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1007/s13205-026-04756-5.