Identification of shared hub genes and pathways between gastric cancer and Helicobacter pylori infection through bioinformatics analysis

Abstract

BackgroundGastric cancer (GC), the third leading cause of cancer-related deaths, has become a worldwide health issue. Gastric cancer is causally associated with Helicobacter pylori (H. pylori) infection. This study characterizes functional genes and critical biological pathways involved in GC and H. pylori infection simultaneously by using bioinformatics approaches. Materials and methodsMicroarray datasets of GC and H. pylori infection diseases were selected from the Gene Expression Omnibus (GEO) public database. So as to discover differentially expressed genes (DEGs), datasets from both diseases (GSE13911, GSE54129, and GSE60427) were examined separately using the GEO2R web tool. Shared DEGs among both conditions were utilized for downstream analyses. Afterward, protein-protein interaction (PPI) networks were generated through the STRING database and visualized via Cytoscape. The degree method was used to define the hub genes using Cytoscape's cytoHubba plug-in. Ultimately, interaction networks for the microRNA (miRNA)-hub genes and transcription factor (TF)-hub genes were evaluated, followed by an analysis of drug-hub gene interactions. ResultsIn this current study, a total of 136 overlapped DEGs, including 101 up- and 35 downregulated genes, were screened between GC and H. pylori infection datasets. The PPI network obtained from the STRING database was subjected to analysis by the Cytoscape's cytoHubba plug-in, and 10 hub genes subsequently were determined using the degree method (which included TLR4, MMP9, ICAM1, CXCL10, CCL4, ITGB2, CXCL1, PTGS2, APOE, and CD80). Based on the obtained results, mir-146a-5p was found to have the highest association with the hub genes among the miRNAs, and RELA was recognized as a TF that regulates most of the hub genes among the TFs. Finally, 104 drugs were identified that might have therapeutic effects on both diseases. ConclusionsThis study provides a new perspective on the genetic association, and molecular pathways between GC and H. pylori infection could result in new treatment methods and diagnostic tests. Further experimental examinations are needed to validate critical genes and biological pathways discovered in this work.