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.
Highlights
Renal cell carcinoma (RCC) is a common cancer of urinary system, accounting for around 4% of all newly diagnosed cancers worldwide (Siegel and Miller, 2021)
The findings displayed that there were 92 differentially expressed antioxidant genes in Kidney renal clear cell carcinoma (KIRC) tissues compared with normal controls, of which 57 were down-regulated and 35 were upregulated (Supplementary Table 2)
The findings suggested that compared with normal tissues, the expression of Dipeptidase 1 (DPEP1), Glutathione S-transferase mu3 (GSTM3), Iodotyrosine deiodinase (IYD), KDM3B, peroxiredoxin 2 (PRDX2), and peroxiredoxin-like 2A (PRXL2A) were all downregulated in KIRC patients (Figure 1)
Summary
Renal cell carcinoma (RCC) is a common cancer of urinary system, accounting for around 4% of all newly diagnosed cancers worldwide (Siegel and Miller, 2021). Kidney renal clear cell carcinoma (KIRC) occupies 70–80% of RCC and is the eighth most common cancer type (Zhao et al, 2018). Asymptomatic patients are found more likely to have progressed to advanced stages which causes high mortality and recurrence rates of RCC. This reasonably indicates the importance of early diagnosis and prognosis evaluation of RCC (Sejima et al, 2013; Zhao et al, 2018).
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