An Oxidative Stress-Related Genes Signature for Predicting Survival in Bladder Cancer: Based on TCGA Database and Bioinformatics

Min Zhang; Gang Du; Zhengtian Li; Dehui Li; Weichao Li; Hening Li; Xingxin Gao; Zhanhong Tang

doi:10.2147/IJGM.S348945

An Oxidative Stress-Related Genes Signature for Predicting Survival in Bladder Cancer: Based on TCGA Database and Bioinformatics

Int J Gen Med. 2022 Mar 8:15:2645-2667. doi: 10.2147/IJGM.S348945. eCollection 2022.

Authors

Min Zhang^#¹, Gang Du^#², Zhengtian Li², Dehui Li³, Weichao Li², Hening Li⁴, Xingxin Gao³, Zhanhong Tang¹

Affiliations

¹ Department of Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People's Republic of China.
² Department of Bone and Joint Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People's Republic of China.
³ Department of Burns and Plastic, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People's Republic of China.
⁴ Guangxi Medical University, Nanning, 530021, People's Republic of China.

^# Contributed equally.

Abstract

Background: Oxidative stress (OS) responses have been linked to oncogenesis and tumor progression and have recently been regarded as a potential strategy for tumor therapy. However, OS-related therapeutic targets have not been identified to date in the bladder cancer (BC).

Methods: The mRNA expression and clinical data of BC were downloaded from the public database. Prognostic risk score signature was constructed using LASSO Cox regression analysis. External validation was performed in GSE15307 cohort. ESTIMATE, CIBERSORT, and ssGSEA algorithm were used to analyze immune cell infiltration and immune microenvironment. Next, functional enrichment analysis was performed to elucidate the mechanism underlying the signature. Additionally, we performed a nomogram to forecast the survival rate of individual BC patients.

Results: An OS-related genes (OSRGs) signature was constructed. Overall survival was lower in the high-risk group than in the low-risk group, according to survival analyses. The area under the curve (AUC) of ROC curves further validated the prognostic signature's strong prediction performance in these two cohorts. The risk score was verified as an independent risk factor for BC by independent prognostic analysis. Moreover, as compared to TNM stage alone, a nomogram that integrated the risk score with TNM stage showed a much superior predictive value. Immune infiltration and tumor microenvironment studies indicated that immune cells and functions may play a significant role in carcinogenesis and development. The levels of expression of prognostic genes were shown to be substantially linked with drug sensitivity.

Conclusion: We developed a novel OSRGs signature for predicting overall survival and impacting the immune status in patients with BC. New nomogram can help clinicians predict the survival rate of BC patients. These findings shed new light on the potential usage of OSRGs signature in BC patients.

Keywords: bladder cancer; drug sensitivity; immune cell infiltration; oxidative stress; prognosis; risk signature.

Grants and funding

This work was financially supported by the National Science Foundation of China (Grant No.81960342), the Natural Science Foundation of Guangxi (Grant No. AB19110030), and the Health Department Fund Project of Guangxi Province (No. z20201184).