CASP4 and CASP8 as newly defined autophagy-pyroptosis-related genes associated with clinical and prognostic features of renal cell carcinoma

Objective: The rapid discoveries of autophagy and pyroptosis have opened new avenues for treating renal cell carcinoma (RCC). The objective was to identify potential autophagy-pyroptosis-related drug targets and plausible prognostic biomarkers crucial for disease detection. Materials and Methods: Gene expression data were downloaded from Gene Expression Omnibus (GSE168845), and autophagy-pyroptosis-related differentially expressed genes (DEGs) were identified. The prognostic values of DEGs were assessed using differential expression analysis and Kaplan-Meier curves, a prognostic nomogram was constructed using the DEG data, and the correlation between DEGs and infiltrating immune cells was evaluated. Additionally, quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) were carried out to verify the expression levels of DEGs. Results: CASP4 and CASP8 were identified as RCC-associated autophagy-pyroptosis-related genes, and CASP4 and CASP8 were found to be highly expressed in RCC tumor tissues. High expression of CASP4 and CASP8 was associated with higher pathological staging and poorer prognosis, whereas a prognostic nomogram constructed based on CASP4 and CASP8 could better predict RCC patient survival rates. Additionally, increased expression of CASP4 and CASP8 was highly correlated with the expression levels of multiple infiltrating immune cell types. Moreover, qRT-PCR and IHC validated the increased expression of CASP4 and CASP8 in RCC. Conclusion: CASP4 and CASP8 were autophagy-pyroptosis-related genes associated with immunotherapy in RCC. CASP4 and CASP8 were identified as potential targets and effective prognostic biomarkers for RCC.