Multidimensional Analysis of PANoptosis-Related Molecule CASP8: Prognostic Significance, Immune Microenvironment Effect, and Therapeutic Implications in Hepatocellular Carcinoma.

BACKGROUNDHepatocellular carcinoma (HCC) presents significant challenges in diagnosis and treatment. Understanding the role of PANoptosis-related molecules in HCC is crucial for advancing therapeutic strategies.

METHODSWe conducted a comprehensive analysis using public data from the Cancer Genome Atlas, Human Protein Atlas, Tumor Immune Single Cell Hub, and STRING databases. Techniques included Kaplan-Meier survival curves, Cox regression, LASSO analysis, and various computational methods for understanding the tumor microenvironment. We also employed ClueGO, gene set enrichment analysis, and other algorithms for biological enrichment analysis.

RESULTSCASP8 emerged as a significant molecule in HCC, correlated with poor survival outcomes. Its expression was predominant in the nucleoplasm and cytosol and varied across different cancer types. Biological enrichment analysis revealed CASP8's association with critical cellular activities and immune responses. In the tumor microenvironment, CASP8 showed correlations with various immune cell types. A nomogram plot was developed for better clinical prognostication. Mutation analysis indicated a higher frequency of TP53 mutations in patients with elevated CASP8 expression. In addition, CASP8 was found to regulate YEATS2 in HCC, highlighting a potential pathway in tumor progression.

CONCLUSIONSOur study underscores the multifaceted role of CASP8 in HCC, emphasizing its prognostic and therapeutic significance. The regulatory relationship between CASP8 and YEATS2 opens new avenues for understanding HCC pathogenesis and treatment strategies.