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

TL;DR

This study identifies a 9-gene autophagy-related signature that predicts breast cancer prognosis and immune exhaustion, offering a new tool for personalized treatment.

Contribution

A novel 9-gene autophagy-related signature is developed for breast cancer prognosis and immune exhaustion prediction.

Findings

The 9-gene signature accurately predicts overall survival in breast cancer patients.

The risk score correlates with selective autophagy pathways and immune-exhausted microenvironment features.

The risk gene MTDH shows increased sensitivity to Vincristine and Gemcitabine.

Abstract

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, P < 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.

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

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