Identification and validation of a ferroptosis-related gene signature predictive of prognosis in breast cancer

Aging (Albany NY). 2021 Sep 9;13(17):21385-21399. doi: 10.18632/aging.203472. Epub 2021 Sep 9.

Abstract

Ferroptosis, a novel form of regulated cell death, is closely associated with the occurrence and development of malignant tumors. Here, we utilized a bioinformatics approach to identify ferroptosis-related genes to establish a robust and reliable prognostic signature in breast cancer (BC). Univariate Cox regression and LASSO regression analyses of patient's survival and gene expression data identified a prognostic signature consisting of 10 ferroptosis-related genes (FRGs). The signature demonstrated a favorable prediction performance, and was validated in two independent datasets, GSE21653 and GSE25066. Analyses of immune infiltrates, tumor microenvironment, immune checkpoints, mutations, drug sensitivity, and clinicopathological features revealed significant differences between low- and high-risk BC patients. A multivariate analysis revealed that the signature was an independent prognostic predictor in BC, and a nomogram combining the risk score and tumor stage intuitively displayed high accuracy and reliability with respect to predicting the survival outcomes of BC patients. These findings indicate that the identified prognostic signature is a potential indicator predictive of prognosis and immunotherapeutic responses in BC patients.

Keywords: breast cancer; ferroptosis; immune cell infiltration; recurrence-free survival; tumor microenvironment.

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / immunology
  • Breast Neoplasms / pathology
  • Case-Control Studies
  • Datasets as Topic
  • Female
  • Ferroptosis / genetics*
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Middle Aged
  • Prognosis
  • Reproducibility of Results
  • Tumor Microenvironment