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| - Methylation, as an epigenetic modification, can affect gene expression and play a role in the occurrence and development of cancer. This research is devoted to discover methylated-differentially expressed genes (MDEGs) in esophageal squamous cell carcinoma (ESCC) and explore special associated pathways. We downloaded GSE51287 methylation profiles and GSE26886 expression profiles from GEO DataSets, and performed a comprehensive bioinformatics analysis. Totally, 19 hypermethylated, lowly expressed genes (Hyper-LGs) were identified, and involved in regulation of cell proliferation, phosphorus metabolic process and protein kinase activity. Meanwhile, 17 hypomethylated, highly expressed genes (Hypo-HGs) were participated in collagen catabolic process, metallopeptidase and cytokine activity. Pathway analysis determined that Hyper-LGs were enriched in arachidonic acid metabolism pathway, while Hypo-HGs were primarily associated with the cytokine-cytokine receptor interaction pathway. IL 6, MMP3, MMP9, SPP1 were identified as hub genes based on the PPI network that combined 7 ranked methods included in cytoHubba, and verification was performed in human tissues. Our integrated analysis identified many novel genetic lesions in ESCC and provides a crucial molecular foundation to improve our understanding of ESCC. Hub genes, including IL 6, MMP3, MMP9 and SPP1, could be considered for use as aberrant methylation-based biomarkers to facilitate the accurate diagnosis and therapy of ESCC.
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