Identification of Key Genes as Potential Drug Targets for Gastric Cancer

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.

Automated summary

This study aimed to identify potential hub-genes and candidate drugs for the treatment of gastric cancer (GC). Differentially expressed genes were identified using next generation sequencing data and a protein-protein interaction network was constructed. Fifteen hub genes were identified, which were associated with important functions and signaling pathways in GC patients. Additionally, six candidate drugs, including Everolimus and Docetaxel, were proposed based on the analysis of key proteins as drug targets.