A Pyroptosis-Related Gene Signature Predicts Prognosis and Reveals Potential Immunotherapy Targets in Kidney Renal Clear Cell Carcinoma

Abstract Background :Kidney renal clear cell carcinoma (KIRC) is a common type of renal cancer with poor prognosis and limited treatment options. Pyroptosis, a non-apoptotic form of cell death, has been shown to regulate tumor microenvironment and impact the prognosis of various cancers, including KIRC. However, the role of pyroptosis-related genes (PRGs) in KIRC remains poorly understood. Therefore, we aimed to construct a PRG signature to predict prognosis and identify potential immunotherapy targets for KIRC patients. Methods: We utilized transcriptomic data from The Cancer Genome Atlas (TCGA) and identified 27 PRGs with prognostic value in KIRC. We used multivariate Cox regression analysis to identify a 5-gene signature (CASP3, CASP4, CHMP3, CHMP4A, and CHMP4C) and divided patients into high-risk and low-risk groups based on their risk scores. We then performed survival analysis and constructed a nomogram to predict the survival probability of KIRC patients. We also performed functional annotation and pathway enrichment analysis of differentially expressed genes (DEGs) between high-risk and low-risk groups to identify potential immunotherapy targets. Results: The 5-gene signature had significant prognostic value in KIRC, as patients in the high-risk group had poorer prognosis and shorter survival time compared to those in the low-risk group. The risk score calculated based on the signature was an independent prognostic factor. The prognostic model had excellent predictive ability, as shown by the ROC analysis and cross-validation. The DEGs between high-risk and low-risk groups were enriched in immune-related pathways,suggesting potential immunotherapy targets for KIRC. Conclusions: We constructed a PRG signature that predicts prognosis and identifies potential immunotherapy targets for KIRC patients. The signature has excellent predictive ability and provides insights into the role of pyroptosis in KIRC. These findings could guide the development of new immunotherapy strategies for KIRC and improve the prognosis of KIRC patients. Trial registration: Not applicable