Identification of Key Genes as Potential Drug Targets for Gastric Cancer

Abstract

Gastric cancer (GC) is one of the most common cancers and ranks the third in cancer mortality all over the world. The goal of this study was to identify potential hub-genes, highlighting their functions, signaling pathways, and candidate drugs for the treatment of GC patients. We used publicly available next generation sequencing (NGS) data to identify differentially expressed (DE) genes. The top DE genes were mapped to STRING database to construct the protein-protein interaction (PPI) network and top hub genes were selected for further analysis. We found a total of 1555 DE genes with 870 upregulated and 685 downregulated genes in GC. We selected the top 400 (200 upregulated and 200 downregulated) genes to construct a PPI network and extracted the top 15 hub genes. The gene ontology (GO) term and kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses of the 15 hub genes exposed some important functions and signaling pathways that were significantly associated with GC patients. The survival analysis of the hub genes disclosed that the lower expressions of the three hub genes CDH2, COL4A1, and COL5A2 were associated with better survival of GC patients. These three genes might be the candidate biomarkers for the diagnosis and treatment of GC. Then, we considered 3 key proteins (genomic biomarkers) (COL4A1, CDH2, and CO5A2) as the drug target proteins (receptors), performed their docking analysis with the 102 meta-drug agents, and found Everolimus, Docetaxel, Lanreotide, Venetoclax, Temsirolimus, and Nilotinib as the top ranked 6 candidate drugs with respect to our proposed target proteins for the treatment against GC patients. Therefore, the proposed drugs might play vital role for the treatment against GC patients.

Robust Identification of Differential Gene Expression Patterns from Multiple Transcriptomics Datasets for Early Diagnosis, Prognosis, and Therapies for Breast Cancer

“…Finally, we recommended our proposed BC-causing five upregulated (COL11A1, COL10A1, CD24, PLK1, UBE2C) and three down-regulated (PDK4, CD36, ACACB) HubGsguided top-ranked six ligands/molecules (Suramin, Rifaximin, Telmisartan, Tukysa Tucatinib, Lynparza Olaparib, TG.02) as the candidate drug molecules by molecular docking analysis. It should be mentioned here that both upregulated and down-regulated HubGs were used as drug targets in different studies [166][167][168][169]. Upregulated HubGs-guided drugs inhibit the upregulation of HubGs, while down-regulated HubGs-guided drugs activate the downregulation of HubGs [170].…”

Current trends and future prospects of drug repositioning in gastrointestinal oncology

“…Furthermore, it has been shown that HC-056456, a CatSper channel blocker, as a novel ferroptosis-inducing compound inhibits GC cell growth by reducing GSH through the p53/SLC7A11 pathway, leading to increased Fe2+ and lipid peroxides in vitro and in vivo ( Zhang et al, 2022b ). In a comprehensive bioinformatic analysis of highly differentially expressed genes in GC, Hossain et al (2023) found that CDH2 , COL4A1 , and COL5A are associated with the survival of GC patients. They also identified docetaxel, lanreotide, venetoclax, temsirolimus, and nilotinib as the top six candidate drugs, targeting aforementioned proteins, for the treatment of GC patients ( Hossain et al, 2023 ).…”

“…In a comprehensive bioinformatic analysis of highly differentially expressed genes in GC, Hossain et al (2023) found that CDH2 , COL4A1 , and COL5A are associated with the survival of GC patients. They also identified docetaxel, lanreotide, venetoclax, temsirolimus, and nilotinib as the top six candidate drugs, targeting aforementioned proteins, for the treatment of GC patients ( Hossain et al, 2023 ). Nitazoxanide also yielded favorable outcomes, as it exhibited activity across GC cell lines tested ( Ribeiro et al, 2023 ).…”