Combining multi-dimensional data to identify key genes and pathways in gastric cancer

Gastric cancer is an aggressive cancer that is often diagnosed late. Early detection and treatment require a better understanding of the molecular pathology of the disease. The present study combined data on gene expression and regulatory levels (microRNA, methylation, copy number) with the aim of identifying key genes and pathways for gastric cancer. Data used in this study was retrieved from The Cancer Genomic Atlas. Differential analyses between gastric cancer and normal tissues were carried out using Limma. Copy number alterations were identified for tumor samples. Bimodal filtering of differentially expressed genes (DEGs) based on regulatory changes was performed to identify candidate genes. Protein–protein interaction networks for candidate genes were generated by Cytoscape software. Gene ontology and pathway analyses were performed, and disease-associated network was constructed using the Agilent literature search plugin on Cytoscape. In total, we identified 3602 DEGs, 251 differentially expressed microRNAs, 604 differential methylation-sites, and 52 copy number altered regions. Three groups of candidate genes controlled by different regulatory mechanisms were screened out. Interaction networks for candidate genes were constructed consisting of 415, 228, and 233 genes, respectively, all of which were enriched in cell cycle, P53 signaling, DNA replication, viral carcinogenesis, HTLV-1 infection, and progesterone mediated oocyte maturation pathways. Nine hub genes (SRC, KAT2B, NR3C1, CDK6, MCM2, PRKDC, BLM, CCNE1, PARK2) were identified that were presumed to be key regulators of the networks; seven of these were shown to be implicated in gastric cancer through disease-associated network construction. The genes and pathways identified in our study may play pivotal roles in gastric carcinogenesis and have clinical significance.