A network-based approach to identify DNA methylation and its involved molecular pathways in testicular germ cell tumors

Background: Testicular germ cell tumors (TGCT) is the most common testicular malignancy threaten young male reproductive health. This study aimed to identify aberrantly methylated-differentially expressed genes and pathways in TGCT by comprehensive bioinformatics analysis. Methods: Data of gene expression microarrays (GSE3218, GSE18155) and gene methylation microarrays (GSE72444) were collected from GEO database. Integrated analysis acquired aberrantly methylated-genes. Functional and pathway enrichment analysis were performed using DAVID database. Protein-protein interaction (PPI) network was constructed by STRING and App Mcode was used for module analysis. GEPIA platform and DiseaseMeth database were used for confirming the expression and methylation levels of hub genes. Finally, Human Protein Atlas database was performed to evaluate the prognostic significance. Results: Totally 604 hypomethylation-high expression and 147 hypermethylation-low genes were identified. The high expressed genes were enriched in biological processes of cell proliferation and migration. The top 8 hub genes of PPI network were GAPDH, VEGFA, PTPRC, RIPK4, MMP9, CSF1R, KRAS and FN1. After validation in GEPIA platform, all hub genes were elevated in TGCT tissues. Only MMP9, CSF1R and PTPRC showed hypomethylation-high expression status, which predicted the poor outcome of TGCT patients. Conclusion: Our study indicated possible aberrantly methylated-differentially expressed genes and pathways in TGCT by bioinformatics analysis, which may provide novel insights for unraveling pathogenesis of TGCT.