Antioxidant Gene Signature Impacts the Immune Infiltration and Predicts the Prognosis of Kidney Renal Clear Cell Carcinoma

Xueting Ren; Li Ma; Nan Wang; Ruina Zhou; Jianhua Wu; Xin Xie; Hao Zhang; Di Liu; Xiaobin Ma; Chengxue Dang; Huafeng Kang; Zhangjian Zhou

doi:10.3389/fgene.2021.721252

Antioxidant Gene Signature Impacts the Immune Infiltration and Predicts the Prognosis of Kidney Renal Clear Cell Carcinoma

Front Genet. 2021 Aug 19:12:721252. doi: 10.3389/fgene.2021.721252. eCollection 2021.

Authors

Xueting Ren¹, Li Ma¹, Nan Wang¹, Ruina Zhou¹, Jianhua Wu¹, Xin Xie², Hao Zhang², Di Liu¹, Xiaobin Ma¹, Chengxue Dang², Huafeng Kang¹, Zhangjian Zhou¹

Affiliations

¹ Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
² Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Abstract

Background: Oxidative stress is related to oncogenic transformation in kidney renal clear cell carcinoma (KIRC). We intended to identify a prognostic antioxidant gene signature and investigate its relationship with immune infiltration in KIRC. Methods: With the support of The Cancer Genome Atlas (TCGA) database, we researched the gene expression and clinical data of KIRC patients. Antioxidant related genes with significant differences in expression between KIRC and normal samples were then identified. Through univariate and multivariate Cox analysis, a prognostic gene model was established and all patients were divided into high- and low-risk subgroups. Single sample gene set enrichment analysis was adopted to analyze the immune infiltration, HLA expression, and immune checkpoint genes in different risk groups. Finally, the prognostic nomogram model was established and evaluated. Results: We identified six antioxidant genes significantly correlated with the outcome of KIRC patients as independent predictors, namely DPEP1 (HR = 0.97, P < 0.05), GSTM3 (HR = 0.97, P < 0.05), IYD (HR = 0.33, P < 0.05), KDM3B (HR = 0.96, P < 0.05), PRDX2 (HR = 0.99, P < 0.05), and PRXL2A (HR = 0.96, P < 0.05). The high- and low-risk subgroups of KIRC patients were grouped according to the six-gene signature. Patients with higher risk scores had poorer prognosis, more advanced grade and stage, and more abundance of M0 macrophages, regulatory T cells, and follicular helper T cells. There were statistically significant differences in HLA and checkpoint gene expression between the two risk subgroups. The performance of the nomogram was favorable (concordance index = 0.766) and reliably predicted the 3-year (AUC = 0.792) and 5-year (AUC = 0.766) survival of patients with KIRC. Conclusion: The novel six antioxidant related gene signature could effectively forecast the prognosis of patients with KIRC, supply insights into the interaction between cellular antioxidant mechanisms and cancer, and is an innovative tool for selecting potential patients and targets for immunotherapy.

Keywords: cellular antioxidant mechanisms; immune infiltration; kidney renal clear cell carcinoma; nomogram; prognosis.