The predictive efficacy of programmed cell death in immunotherapy of melanoma: A comprehensive analysis of gene expression data for programmed cell death biomarker and therapeutic target discovery

Abstract In this study, genes linked to prognosis in skin cutaneous melanoma (SKCM) involved in programmed cell death (PCD) were identified and confirmed and prognostic models based on these genes were constructed. Acquisition and analysis of clinical data and RNA sequencing information from The Cancer Genome Atlas‐SKCM (TCGA‐SKCM) and Sangerbox databases, gene expression data for 477 tumor samples and 2 normal samples were successfully gathered. The patients were separated into two clusters based on consensus clustering of PCD‐related genes, with Cluster A having greater tumor purity, ESTIMATE score, immune score, and matrix score, and Cluster B having a significantly distinct pattern of immune cell infiltration. The use of gene set enrichment analysis and weighted correlation network analysis showed significant associations between certain genes and factors such as tumor mutation burden, age, stage, grade, and tumor subtype. Finally, based on the 12 genes selected by Least Absolute Shrinkage and Selection Operator regression analysis (STAT3, IRF2, SLC7A11, ZEB1, LIPT1, PML, GCH1, GYS1, ABCC1, XBP1, TFAP2C, NOX4), a prognostic model of PGD‐related genes was constructed. The effectiveness of the model's prognostic value was confirmed through survival analysis, time‐dependent receiver operating characteristic curve, single‐factor Cox regression analysis, and nomogram. We also verified the relationship between the GCH1 and MKI67 expression by wet experiment. This model has high prediction accuracy in SKCM patients and can provide a reference for clinical treatment.