A Novel Pyroptosis-Related Gene Signature for Predicting Prognosis in Kidney Renal Papillary Cell Carcinoma

Abstract

Pyroptosis is defined as an inflammatory form of programmed cell death. Increasing studies have demonstrated that pyroptosis is closely related to tumor development and antitumor process. However, the role of pyroptosis in kidney renal papillary cell carcinoma (KIRP) remains obscure. In this study, we analyzed the expression of 52 pyroptosis-related genes (PRGs) in KIRP, of which 20 differentially expressed PRGs were identified between tumor and normal tissues. Consensus clustering analysis based on these PRGs was used to divided patients into two clusters, from which a significant difference in survival was found (p = 0.0041). The prognostic risk model based on six PRGs (CASP8, CASP9, CHMP2A, GPX4, IL6, and IRF1) was built using univariate Cox regression and LASSO–Cox regression analysis, with good performance in predicting one-, three-, and five-year overall survival. Kaplan–Meier survival analysis showed that the high-risk group had a poor survival outcome (p < 0.001) and risk score was an independent prognostic factor (HR: 2.655, 95% CI 1.192–5.911, p = 0.016). Immune profiling revealed differences in immune cell infiltration between the two groups, and the infiltration of M2 macrophages was significantly upregulated in the tumor immune microenvironment, implying that tumor immunity participated in the KIRP progression. Finally, we identified two hub genes in tumor tissues (IL6 and CASP9), which were validated in vitro. In conclusion, we conducted a comprehensive analysis of PRGs in KIRP and tried to provide a pyroptosis-related signature for predicting the prognosis.

Development and implementation of a prognostic model for clear cell renal cell carcinoma based on heterogeneous TLR4 expression

“…Past research has employed consensus clustering to analyse gene expression data of kidney cancer. For instance, studies have explored gene expression related to ferroptosis in clear cell renal cell carcinoma [ 19 ], while in renal papillary cell carcinoma, gene expression associated with flame cell death has been researched [ 20 ]. Moreover, another study described the role of serine metabolism in papillary renal cell carcinoma and reported its relationship with tumour progression and immune suppression [ 21 ].…”