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.

Key Roles of p53 Signaling Pathway-Related Factors GADD45B and SERPINE1 in the Occurrence and Development of Gastric Cancer

“…Owing to the high incidence and mortality of GC, it is urgent to understand its underlying molecular mechanism to discover new biomarkers [ 17 ]. DEGs between GC and adjacent tissues are identified from TCGA and GTEx databases [ 18 ]. This study aimed to explore and verify the possible key factors in the p53 signaling pathway that participated in the initiation and progression of GC using GTEx and TCGA databases.…”

LPCAT1 enhances the invasion and migration in gastric cancer: Based on computational biology methods and in vitro experiments

“…The latest statistics from the American Cancer Society showed that approximately 26,380 new cases of GC are projected to occur in 2022, of which 11,090 cases are likely to result in death 4 . In terms of treatment technology, although neoadjuvant chemoradiotherapy and targeting therapy are believed to be effective, surgery has proven to be the sole radical treatment 5–8 . Contemporarily, the survival rate of patients with early GC was more than 95% owing to surgical improvements, the development of chemotherapy and radiotherapy, and the practice of neoadjuvant treatments.…”

“… 4 In terms of treatment technology, although neoadjuvant chemoradiotherapy and targeting therapy are believed to be effective, surgery has proven to be the sole radical treatment. 5 , 6 , 7 , 8 Contemporarily, the survival rate of patients with early GC was more than 95% owing to surgical improvements, the development of chemotherapy and radiotherapy, and the practice of neoadjuvant treatments. Nevertheless, the difficulty with early detection has led to the fact that the majority of patients have been diagnosed at late stages and have thus failed to undergo optimal surgical treatment.…”