Potential Application of Pyroptosis in Kidney Renal Clear Cell Carcinoma Immunotherapy and Targeted Therapy

Front Pharmacol. 2022 Jun 15:13:918647. doi: 10.3389/fphar.2022.918647. eCollection 2022.

Abstract

Renal cell carcinoma (RCC) is a type of cancer with an increasing rate of morbidity and mortality and is a serious threat to human health. The treatment of RCC, especially kidney renal clear cell carcinoma (KIRC), has always been the focus of clinical treatment. Using The Cancer Genome Atlas (TCGA) database as a starting point, we explored the feasibility of applying the pyroptosis mechanism to KIRC treatment by searching for cancer markers associated with pyroptosis and cancer treatment signatures. The obtained samples were clustered using unsupervised clustering analysis to define the different KIRC subtypes with different pyroptosis expression levels. Based on this, a gene expression analysis was performed to explore the carcinogenic mechanism that is markedly related to pyroptosis. The Genomics of Drug Sensitivity in Cancer database and single sample gene set enrichment analysis (ssGSEA) algorithm were used to analyze the different treatment methods of the current prominent KIRC to determine whether pyroptosis plays a role. Finally, LASSO regression was used to screen for related genes and construct a model to predict patient prognosis. The expression levels of GSDME, CASP3, CASP4, CASP5, CHMP3, and CHMP4C were incorporated into the model construction. After verification, the prediction accuracy of the 3-, 5-, 7- and 10 years survival rates of our prognostic model were 0.66, 0.701, 0.719, and 0.728, respectively. Through the above analysis, we demonstrated the feasibility of pyroptosis in the clinical treatment of KIRC and provided novel ideas and suggestions for the clinical treatment of KIRC.

Keywords: KIRC; RCD; bioinformatics analysis; prognostic model; pyroptosis.