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

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.

Comprehensive analysis of the glutathione S-transferase Mu (GSTM) gene family in ovarian cancer identifies prognostic and expression significance

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A web-based calculator for predicting the prognosis of patients with sarcoma on the basis of antioxidant gene signatures

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Identification of epigenetic dysregulation gene markers and immune landscape in kidney renal clear cell carcinoma by comprehensive genomic analysis

“…After referring to the literature, we finally selected 4 prognostic-related risk models, namely, 9-gene signature (Zhong) ( 38 ), 7-gene signature (Jiang) ( 39 ), 7-gene signature (Chen) ( 40 ), and 6-gene signature (Ren) ( 41 ), for comparing the prediction performance with our 8-gene model. To make the model comparable, we calculated the riskscore of each KIRC sample in the TCGA using the same method based on the corresponding genes in the 4 models.…”