javad arabpour - Young Researchers and Elite Club, Tehran Medical Sciences, IslamicAzad University, Tehran ۱۹۴۹۶۳۵۸۸۱, Iran
reza maddah - Department of Bioprocess Engineering, Institute of Industrial andEnvironmental Biotechnology, National Institute of Genetic Engineeringand Biotechnology, Tehran, Iran

Background: Gastric cancer (GC) is the third leading causeof cancer-related deaths worldwide and is causally associatedwith Helicobacter pylori (H. pylori) infection. This study aimedto identify the functional genes and critical biological pathwaysinvolved in both GC and H. pylori infection using bioinformaticsapproaches.Materials and Methods: To identify differentially expressedgenes (DEGs), we selected microarray datasets from the GeneExpression Omnibus (GEO) public database for both gastriccancer (GC) and Helicobacter pylori (H. pylori) infection.These datasets, which included GSE۱۳۹۱۱ (GC), GSE۵۴۱۲۹(GC), and GSE۶۰۴۲۷ (H. pylori infection), were individuallyanalyzed using the GEO۲R web tool. Shared DEGs amongdatasets were then analyzed using protein-protein interaction(PPI) networks generated from the STRING database and visualizedvia Cytoscape. Hub genes were defined using the degreemethod in Cytoscape's cytoHubba plug-in, and interactionnetworks for microRNA (miRNA)-hub genes and transcriptionfactor (TF)-hub genes were evaluated.Results: A total of ۱۳۶ DEGs, including ۱۰۱ up- and ۳۵ downregulatedgenes, were screened between GC and H. pylori infectiondatasets. The PPI network obtained from the STRINGdatabase was analyzed using the Cytoscape's cytoHubba plugin,and ۱۰ hub genes were identified using the degree method,including TLR۴, MMP۹, ICAM۱, CXCL۱۰, CCL۴, ITGB۲,CXCL۱, PTGS۲, APOE, and CD۸۰. Among the miRNAs, mir-۱۴۶a-۵p was found to have the highest association with the hubgenes, and RELA was recognized as the TF that regulates mostof the hub genes among the TFs.Conclusion: This study provides new insights into the geneticassociations and molecular pathways between GC and H. pyloriinfection, which could lead to the development of new treatmentmethods and diagnostic tests. However, further experimental experimentalvalidations are needed to confirm the critical genes andbiological pathways identified in this study.

Gastric cancer, Helicobacter pylori infection, Differentiallyexpressed genes, Protein-protein interaction network,Bioinformatics analysis