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Open Access

Identification of Key Genes as Potential Drug Targets for Gastric Cancer

Center for High Performance Computing, Joint Engineering Research Center for Health Big Data Intelligent Analysis Technology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
School of Computer Science and Technology, University of Chinese Academy of Sciences, Beijing 100049, China
Department of Statistics, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh
Guangdong Provincial Key Laboratory for Genome Stability and Disease Prevention and Regional Immunity and Diseases, Department of Pathology, Shenzhen University, Shenzhen 518060, China

Md. Tofazzal Hossain and Md. Selim Reza contribute equally to this paper.

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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.

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Tsinghua Science and Technology
Pages 649-664

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Cite this article:
Hossain MT, Reza MS, Peng Y, et al. Identification of Key Genes as Potential Drug Targets for Gastric Cancer. Tsinghua Science and Technology, 2023, 28(4): 649-664. https://doi.org/10.26599/TST.2022.9010035

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Received: 18 February 2022
Revised: 31 May 2022
Accepted: 29 August 2022
Published: 06 January 2023
© The author(s) 2023.

The articles published in this open access journal are distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).