Identification of DNA methylation-regulated differentially-expressed genes and related pathways using Illumina 450K BeadChip and bioinformatic analysis in gastric cancer

In the current research, we aimed to identify and analyze methylation-regulated differentially-expressed genes (MeDEGs) and related pathways using bioinformatic methods. We downloaded RNA-seq, Illumina Human Methylation 450 K BeadChip and clinical information of gastric cancer (GC) from The Cancer Genome Atlas (TCGA) project. Differentially-expressed genes (DEGs) were identified using the edgeR package. Then, we performed Spearman's correlation analysis between DEG expression levels and methylation levels. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed in the DAVID database. We then conducted Kaplan-Meier survival analysis to explore the relationship between methylation, expression and prognosis. The protein-protein interaction networks were further analyzed using the STRING database. A total of 204 down-regulated DEGs and 164 up-regulated DEGs were identified as MeDEGs. GO and KEGG pathway analyses showed that MeDEGs were enriched in multiple cancer-related terms. Kaplan-Meier survival analysis showed that eight up-regulated MeDEGs (CAMKV, COMP, FGF3, FGF19, FOXL2, IGF2BP1, IGFBP1 and NPPB) and five down-regulated MeDEGs (ALDH3B2, CALML3, FLRT1, G6PC and HRASLS2) were associated with prognosis of GC patients. In addition, PPI networks and KEGG pathway analyses further confirmed the critical role of prognosis-related MeDEGs. In conclusion, methylation plays a critical role in GC progression. Multiple MeDEGs are related to prognosis, suggesting that they may be potential targets in tumor treatment.