Informatics in Medicine Unlocked (Jan 2021)

Revealing novel biomarkers involved in development and progression of gastric cancer by comprehensive bioinformatics analysis

  • Homa Akhavan,
  • Sina Ramezani,
  • Zinat Shams,
  • Saied Hosseini-Asl

Journal volume & issue
Vol. 25
p. 100630

Abstract

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Gastric cancer (GC) is the third cause of cancer mortality in the world but the molecular mechanisms underlying the pathogenesis of GC remain little known. This study aimed to provide novel insights into GC tumorigenesis and identify potential key genes for the clinical management of patients through comprehensive bioinformatics analysis. mRNA (GSE26942, GSE66229, and GSE54129) and miRNA (GSE26595) microarray datasets were downloaded and Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEmiRs) were obtained using R software. The FunRich database was applied to analyze the function and pathways enrichment of DEGs. Protein-protein interaction (PPI) network was assessed using STRING and visualized by Cytoscape software. Then, the value of key genes were validated. There were 516 DEGs that overlapped in three expression profile datasets and predicted targets of DEmiRs. DEGs were mainly enriched in biological processes related to apoptosis and regulation of nucleobase, nucleoside, nucleotide, and nucleic acid metabolism. Pathway analysis illustrated that DEGs were enriched in P53 signaling pathway, pathways in cancer, PI3K-AKT signaling pathway, small cell lung cancer, MicroRNAs in cancer, and apoptosis. We identified 5 genes (CEMIP, CLDN1, SERPINE1, PMEPA1, and LIFR) that were common amongst all three datasets and predicted targets of DEmiRs, with a good performance in predicting overall survivals. Furthermore, we constructed miRNAs–mRNAs network, which revealed miRNAs and genes involved in the development and progression of GC, including hsa-miR-421, hsa-miR-193a-3p, hsa-miR-576–5p, hsa-miR-1246, CTC1, RGMB, E2F6, IGF1, JARID2, and PHKA1. The findings of this study improved the understanding of molecular mechanisms of GC and the roles of identified DEmiRs in GC through interactions with DEGs may provide potential targets for GC diagnosis and treatment.

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