Identification of differentially expressed methylated genes in melanoma versus nevi using bioinformatics methods

Melanoma is a highly invasive malignant skin tumor. While melanoma may share some similarities with that of melanocytic nevi, there also exist a number of distinct differences between these conditions. An analysis of these differences may provide a means to more effectively evaluate the etiology and pathogenesis of melanoma. In particular, differences in aberrant methylation expression may prove to represent a critical distinction.

Data from gene expression datasets (GSE3189 and GSE46517) and gene methylation datasets (GSE86355 and GSE120878) were downloaded from the GEO database. GEO2R was used to obtain differentially expressed genes (DEGs) and differentially methylation genes (DMGs). Function and pathway enrichment of selected genes were performed using the DAVID database. A protein-protein interaction (PPI) network was constructed by STRING while its visualization was achieved with use of cytoscape. Primary melanoma samples from TCGA were used to identify significant survival genes.

There was a total of 199 genes in the hypermethylation-low expression group, while 136 genes in the hypomethylation-high expression group were identified. The former were enriched in the biological processes of transcription regulation, RNA metabolism and regulation of cell proliferation. The later were highly involved in cell cycle regulation. 13 genes were screened out after survival analysis and included: ISG20, DTL, TRPV2, PLOD3, KIF3C, DLGAP4, PI4K2A, WIPI1, SHANK2, SLC16A10, GSTA4O, LFML2A and TMEM47.

These findings reveal some of the methylated differentially expressed genes and pathways that exist between melonoma and melanocytic nevi. Moreover, we have identified some critical genes that may help to improve the diagnosis and treatment of melanoma.