Identification of putative drugs for gastric adenocarcinoma utilizing differentially expressed genes and connectivity map.

Abstract

Gastric adenocarcinoma (GAC) is a challenging disease with dim prognosis even after surgery; hence, novel treatments for GAC are in urgent need. The aim of the present study was to explore new potential compounds interfering with the key pathways related to GAC progression. The differentially expressed genes (DEGs) between GAC and adjacent tissues were identified from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database. Connectivity Map (CMap) was performed to screen candidate compounds for treating GAC. Subsequently, pathways affected by compounds were overlapped with those enriched by the DEGs to further identify compounds which had anti-GAC potential. A total of 843 DEGs of GAC were identified. Via Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, 13 pathways were significantly enriched. Moreover, 78 compounds with markedly negative correlations with DEGs were revealed in CMap database (P<0.05 and Enrichment <0). Subpathways of cell cycle and p53 signaling pathways, and core genes of these compounds, cyclin B1 (CCNB1) and CDC6, were identified. This study further revealed seven compounds that may be effective against GAC; in particular methylbenzethonium chloride and alexidine have never yet been reported for GAC treatment. In brief, the candidate drugs identified in this study may provide new options to improve the treatment of patients with GAC. However, the biological effects of these drugs need further investigation.