Integrated Analysis of DNA Copy Number Changes and Gene Expression Identifies Key Genes in Gastric Cancer.

Abstract

This study was aimed at identifying differentially expressed genes (DEGs) with copy number changes in gastric cancer (GC) pathogenesis. Microarray data GSE33429, including array-based comparative genomic hybridization and gene expression profiles, were obtained. DEGs were screened between GC and adjacent noncancerous tissues. Genes located at Minimum Common Regions (MCRs) were identified, and overlapped genes between DEGs and genes with amplification or deletion were identified. Gene Ontology function and pathway enrichment analysis of DEGs were performed. A protein-protein interaction network for DEGs was built, and significant modules were mined from the network. Functional annotation of genes in modules was also performed. A total of 677 up- and 583 downregulated DEGs were identified, including 37 overexpressed genes located at gained MCRs and 28 downregulated genes located at deleted MCRs. In significant modules, upregulated genes with amplification, including DSN1 (MIS12 kinetochore complex component), MAPRE1 (microtubule-associated protein, RP/EB family, member 1), TPX2 (microtubule-associated), UBE2C (ubiquitin-conjugating enzyme E2C), and MYBL2 (v-myb avian myeloblastosis viral oncogene homolog-like 2), were associated with cell cycle, but downregulated genes with deletion, including UGT2B15 (UDP glucuronosyltransferase 2 family, polypeptide B15), UGT2B17 (UDP glucuronosyltransferase 2 family, polypeptide B17), ADH1B (alcohol dehydrogenase 1B), and ADH1A (alcohol dehydrogenase 1A), were related to metabolism. The identified genes DSN1, MAPRE1, TPX2, UBE2C, and MYBL2 located at gained MCRs and UGT2B15, UGT2B17, ADH1B, and ADH1A located at deleted MCRs may play an important role in GC progression through regulating cell cycle and metabolism.