Identification and validation of a robust autophagy-related molecular model for predicting the prognosis of breast cancer patients

Aging (Albany NY). 2021 Jun 29;13(12):16684-16695. doi: 10.18632/aging.203187. Epub 2021 Jun 29.

Abstract

Despite a relatively low mortality rate, high recurrence rates represent a significant problem for breast cancer (BC) patients. Autophagy affects the development, progression, and prognosis of various cancers, including BC. The aim of the present study was to identify candidate autophagy-related genes (ARGs) and construct a molecular-clinicopathological signature to predict recurrence risk in BC. A 10-ARG-based signature was established in a training cohort (GEO-BC dataset GSE25066) with LASSO Cox regression and assessed in an independent validation cohort (GEO-BC GSE22219). Significant differences in recurrence-free survival were observed for high- and low-risk patients segregated based on their signature-based risk score. Time-dependent receiver operating characteristic (tdROC) analysis of signature performance demonstrated satisfactory accuracy and predictive power in both the training and validation cohorts. Moreover, we developed a nomogram to predict 3- and 5-year recurrence-free survival by combining the autophagy-related risk score and clinicopathological data. Both the tdROC and calibration curves indicated high discriminating ability for the nomogram. This study indicates that our ARG-based signature is an independent prognostic classifier for recurrence-free survival in BC. In addition, individualized survival risk assessment and treatment decisions might be effectively improved by implementing the proposed nomogram.

Keywords: GEO; autophagy; breast cancer; risk.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Area Under Curve
  • Autophagy* / genetics
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Calibration
  • Disease-Free Survival
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Middle Aged
  • Models, Molecular*
  • Nomograms
  • Prognosis
  • ROC Curve
  • Reproducibility of Results
  • Time Factors