Genetic and Epigenetic Changes in Melanoma Progression: A TCGA-based Study

We aimed to investigate molecular mechanisms affecting melanoma progression by comparing genetic/epigenetic features between melanomas of different Breslow thickness and stage using TCGA (The Cancer Genome Atlas) data. The TCGA, Firehose Legacy, melanoma data set was utilized on the cBioPortal website. The cases were compared in terms of mRNA expression and DNA methylation. Gene Ontology (GO) and KEGG pathways enrichment analysis were performed using the online WebGestalt tool. STRING and Cytoscape software were used to construct a protein-protein interaction network and identify hub genes. P and q <0.05, FDR< 0.05 were considered statistically significant. 1001 differentially expressed genes were identified between thin (≤1 mm) and thick (>1 mm) melanomas. Pathway analyses revealed that genes enriched in thin melanomas were associated with adaptive immune response, T-cell activation, immune response regulation, leukocyte, and cytokine-related pathways, whereas genes enriched in thick melanomas were related to epidermis development. Ten hub genes were identified ( CD4, IFNG, PTPRC, CD8A, CTLA4, CD69, ICOS, CD27, CD28, CD19 ). All of these genes are involved in crucial immunological processes. Understanding the complex changes in melanoma progression is essential for accurate diagnosis and prediction of prognosis. Our results may shed light on subsequent studies to identify the steps in melanoma progression.