A Newly Defined Pyroptosis-Related Gene Signature for the Prognosis of Bladder Cancer

Weikang Chen,1,&ast; Wenhao Zhang,2,3,&ast; Tao Zhou,1,&ast; Jian Cai,1 Zhixian Yu,1 Zhigang Wu1 1Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China; 2The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 325000, People’s Republic of China; 3Department of Urology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 325000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhixian Yu; Zhigang WuDepartment of Urology, The First Affiliated Hospital of Wenzhou Medical University, No. 2, Fuxue Road Lucheng District, Wenzhou, Zhejiang, 325000, People’s Republic of ChinaEmail yuzx515@163.com; andrologywzg@wmu.edu.cnBackground: Bladder cancer (BC), as the most common urinary system tumor type and the main cause of tumor-related death, has an unsatisfactory prognosis. In recent years, related literature has proposed that cell pyroptosis is an inflammatory form of programmed cell death. However, in BC, the relationship between the expression of pyroptosis-related genes and the prognosis has not been elucidated.Methods: We got the RNA sequencing data from TCGA and GEO datasets. Fifty-two pyroptosis-related genes were extracted for further explore. Then, we compared the gene expression levels between the normal bladder and BC tissues. After that, we develop and validate a pyroptosis-related gene prognostic model and made following functional enrichment analysis and single-sample gene set enrichment analysis of the differentially expressed genes between the high- and low-risk groups.Results: Twenty-nine differentially expressed genes (DEGs) were found between normal and tumor tissues. Based on the median score calculated by the risk score formula from 8 pyroptosis-related genes, 414 patients were equally divided into low- and high-risk subgroups. The survival probability of BC patients in the high-risk group was significantly lower than that in the low-risk group (P < 0.001). Through multivariate analysis, our risk score is an independent factor predicting OS in BC patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis show that high-risk populations are rich in immune-related genes and have a decreased immune status. All the above results have been externally verified from GEO cohort.Conclusion: Pyroptosis-related genes are closely related to tumor immunity and are a potential prognostic tool for predicting BCs.Keywords: pyroptosis, bladder cancer, immune, prognosis, TCG