Abstract
Background: PANoptosis, a recently identified pathway of cell death, entails interplay and coordination among pyroptosis, apoptosis, and necroptosis mechanisms. Yet, the prognostic implications of PANoptosis-related genes (PRGs) in clear cell renal cell carcinoma (ccRCC) remain largely unexplored.
Methods: In this study, nineteen PANoptosis-related genes (PRGs) were identified from prior research, and clinical data of patients with clear cell renal cell carcinoma (ccRCC) were retrieved from TCGA. In the training cohort, we conducted univariate Cox, Lasso, and multivariate Cox regression analyses to identify prognostic PANoptosis-related genes (PRGs) and subsequently develop a prognostic PRGs signature. The prognostic signature was validated using both the testing cohort and the entire cohort. Furthermore, a nomogram was developed to predict prognosis at various clinicopathological stages and risk scores. Additionally, a network comprising 6 prognosis-related differentially expressed genes (PRDEGs) and 5 predicted functional partners was constructed.
Results: We utilized univariate Cox analysis to assess the prognostic significance of the 19 PANoptosis-related genes (PRGs). Subsequently, we employed both the least absolute shrinkage and selection operator (Lasso) and multivariate Cox analysis to further evaluate the prognostic value of these PRGs. We established a prognostic risk model consisting of six PRDEGs: TAB2, TAB3, TNFAIP3, CASP7, AIM2, and TRADD. Kaplan-Meier (KM) analysis and time-related receiver operating characteristic (ROC) curve analysis were performed to evaluate overall survival and compare high- and low-risk groups. Incorporating clinicopathological characteristics, the risk model was validated as a novel independent prognostic factor for clear cell renal cell carcinoma through univariate and multivariate Cox regression analyses. Furthermore, the nomogram demonstrated reliable predictive ability.
Conclusion: The signature comprising six PRDEGs showed notable prognostic significance for ccRCC. These genes hold promise as potential therapeutic targets in clinical settings.