# 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.

## Key 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.