Research Paper Volume 13, Issue 12 pp 16713—16732

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

Yin Weijiao1,2, , Liao Fuchun1, , Chen Mengjie1, , Qin Xiaoqing1, , Lai Hao3, , Lin Yuan3, , Yao Desheng1, ,

  • 1 Department of Gynecologic Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region 530021, PR China
  • 2 Henan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology, Luoyang, PR China
  • 3 Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region 530021, PR China

Received: March 24, 2021       Accepted: June 4, 2021       Published: June 24, 2021      

https://doi.org/10.18632/aging.203190
How to Cite

Copyright: © 2021 Weijiao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.

Abbreviations

EC: endometrial cancer; FRGs: ferroptosis-related genes; UCEC: uterine corpus endometrial carcinoma; TCGA: The Cancer Genome Atlas; DEGs: differentially expressed genes; LASSO: the least absolute shrinkage and selection operator; ROC: receiver operating characteristic curve; PCA: principal components analyses; AUC: Area Under Curve; FDR: false discovery rate; KEGG: Kyoto Encyclopedia of Genes and Genomes; PI: prognostic index; TIICs: tumor-infiltrating immune cells; ssGSEA: single-sample gene set enrichment analysis; HPA: the human protein atlas; Tregs: T cells regulatory; DCs: dendritic cells; aDCs: activated DCs; iDCs: immature DCs; pDCs: plasmacytoid DCs; Tem: effector memory T cell; Tcm: central memory T cell; IFN: interferon; APC: antigen presenting cell.