Immune infiltration and a ferroptosis-associated gene signature for predicting the prognosis of patients with endometrial cancer

Aging (Albany NY). 2021 Jun 24;13(12):16713-16732. doi: 10.18632/aging.203190. Epub 2021 Jun 24.

Abstract

Ferroptosis, a form of programmed cell death induced by excess iron-dependent lipid peroxidation product accumulation, plays a critical role in cancer. However, there are few reports about ferroptosis in endometrial cancer (EC). This article explores the relationship between ferroptosis-related gene (FRG) expression and prognosis in EC patients. One hundred thirty-five FRGs were obtained by mining the literature, retrieving GeneCards and analyzing 552 malignant uterine corpus endometrial carcinoma (UCEC) samples, which were randomly assigned to training and testing groups (1:1 ratio), and 23 normal samples from The Cancer Genome Atlas (TCGA). We established a signature using eight screened FRGs (MDM2, GPX4, PRKAA2, PRNP, SLC11A2, ATP5MC3, PHKG2 and ACO1) related to overall survival using LASSO regression analysis. The samples were divided into low- and high-risk subgroups according to the median risk score. Kaplan-Meier survival curves showed that the low-risk group had better OS. ROC curves showed that this signature performed well in predicting OS (1-, 2-, 3-, and 5-year AUCs of 0.676, 0.775, 0.797, and 0.826, respectively). We systematically analyzed the immune infiltrating profile in UCEC samples from TCGA. Overall, our study identified a novel prognostic signature of 8 FRGs that can potentially predict the prognosis of EC.

Keywords: endometrial cancer; ferroptosis; prognosis.

MeSH terms

  • Cohort Studies
  • Databases, Genetic
  • Endometrial Neoplasms / genetics*
  • Endometrial Neoplasms / immunology*
  • Female
  • Ferroptosis / genetics*
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic
  • Genetic Variation
  • Humans
  • Lymphocytes, Tumor-Infiltrating / metabolism*
  • Molecular Sequence Annotation
  • Principal Component Analysis
  • Prognosis
  • Protein Interaction Maps / genetics
  • Reproducibility of Results
  • Risk Factors