Melanoma is the most deadly type of skin cancer. This study aimed at uncovering the molecular mechanisms underlying melanoma progression. This study used the microarray dataset GSE46517, downloaded from the Gene Expression Omnibus database, including eight normal tissue samples, nine nevus tissue samples, 31 primary melanoma samples, and 73 metastatic melanoma tissue samples. Differentially expressed genes (DEGs) in nevus, primary melanoma, and metastatic melanoma were identified, with which a reactome functional interaction (FI) network was constructed, and pathway enrichment analysis of the network modules was performed. The common DEGs in primary and metastatic melanoma were identified by venn diagram analysis, followed by Gene ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and a protein–protein interaction (PPI) network. The study identified 130 DEGs in nevus, 539 DEGs in primary melanoma, and 1170 DEGs in metastatic melanoma. The reactome FI network modules 10, 14, and 15 were significantly enriched in the transforming growth factor (TGF)-β signaling pathway. EDNRB, MITF, and LEF1 were the common upregulated DEGs in nevus, primary, and metastatic melanoma, and they were significantly enriched in the melanogenesis pathway. In the PPI network with the common DEGs in primary and metastatic melanoma, EGFR, ERBB2, CD8A, and MMP9 were the hub genes. EDNRB, MITF, LEF1, EGFR, ERBB2, CD8A, MMP9, melanogenesis pathway, and TGF-β signaling pathway might be involved in the molecular mechanism of melanoma. These genes may be recommended as promising molecular targets for development of melanoma therapeutics.
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