Cutaneous melanoma (CM) is a highly aggressive skin malignancy with marked molecular heterogeneity and poor prognosis. Pyroptosis, an inflammatory form of programmed cell death, has been implicated in tumor progression and immune regulation; however, its prognostic value in CM remains incompletely understood. Gene expression data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas skin cutaneous melanoma (TCGA-SKCM) cohorts were analyzed to identify pyroptosis-related differentially expressed genes (PRGs). Eight CM-associated PRGs were identified through integrated differential expression and intersection analyses. Functional enrichment analyses revealed that these genes were involved in inflammatory responses, immune regulation, and cell cycle-related pathways. A prognostic model was constructed using univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses in the TCGA-SKCM cohort. Six PRGs were incorporated into the prognostic signature, of which ISG15, GZMB, and EGFR were independently associated with patient survival. The model demonstrated good predictive performance, as confirmed by receiver operating characteristic curves, Kaplan-Meier survival analysis, calibration plots, and decision curve analysis at 1-, 3-, and 5-year time points. Immune infiltration analysis revealed that ISG15, GZMB, and EGFR expression were positively correlated with the enrichment of multiple immune cell populations. Mutation profiling further supported the clinical relevance of these prognostic genes. In summary, we developed a pyroptosis-related prognostic model for cutaneous melanoma and identified ISG15, GZMB, and EGFR as clinically relevant prognostic biomarkers. Our findings enhance the understanding of pyroptosis-associated molecular mechanisms in CM and support their potential utility in prognostic stratification.
Jiang et al. (2026) studied this question.