A novel oxidative stress-related genes signature associated with clinical prognosis and immunotherapy responses in clear cell renal cell carcinoma

Frontiers in Oncology

Oncology

Fenghua Li¹  Bin Fu²  Binbin Gong²  Xin Wu²  Lianmin Luo²  Weimin Chen²  Libo Zhou²  Wenjie Xie² 

[1] Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China;Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China;

关键词: clear cell renal cell carcinoma;    oxidative stress;    mRNA;    prognosis signature;    immune microenvironment;    immunotherapy;   

DOI  :  10.3389/fonc.2023.1184841

 received in 2023-03-12, accepted in 2023-06-26,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundOxidative stress plays a significant role in the tumorigenesis and progression of tumors. We aimed to develop a prognostic signature using oxidative stress-related genes (ORGs) to predict clinical outcome and provide light on the immunotherapy responses of clear cell renal cell carcinoma (ccRCC).MethodsThe information of ccRCC patients were collected from the TCGA and the E-MTAB-1980 datasets. Univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) were conducted to screen out overall survival (OS)-related genes. Then, an ORGs risk signature was built by multivariate Cox regression analyses. The performance of the risk signature was evaluated with Kaplan-Meier (K-M) survival. The ssGSEA and CIBERSORT algorithms were performed to evaluate immune infiltration status. Finally, immunotherapy responses was analyzed based on expression of several immune checkpoints.ResultsA prognostic 9-gene signature with ABCB1, AGER, E2F1, FOXM1, HADH, ISG15, KCNMA1, PLG, and TEK. The patients in the high risk group had apparently poor survival (TCGA: p < 0.001; E-MTAB-1980: p < 0.001). The AUC of the signature was 0.81 at 1 year, 0.76 at 3 years, and 0.78 at 5 years in the TCGA, respectively, and was 0.8 at 1 year, 0.82 at 3 years, and 0.83 at 5 years in the E-MTAB-1980, respectively. Independent prognostic analysis proved the stable clinical prognostic value of the signature (TCGA cohort: HR = 1.188, 95% CI =1.142-1.236, p < 0.001; E-MTAB-1980 cohort: HR =1.877, 95% CI= 1.377-2.588, p < 0.001). Clinical features correlation analysis proved that patients in the high risk group were more likely to have a larger range of clinical tumor progression. The ssGSEA and CIBERSORT analysis indicated that immune infiltration status were significantly different between two risk groups. Finally, we found that patients in the high risk group tended to respond more actively to immunotherapy.ConclusionWe developed a robust prognostic signature based on ORGs, which may contribute to predict survival and guide personalize immunotherapy of individuals with ccRCC.

【 授权许可】

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Copyright © 2023 Wu, Li, Xie, Gong, Fu, Chen, Zhou and Luo