• Prediction of Immune-Related Genes and pathways in Gastric adenocarcinoma through systems biology approach
  • Nafiseh Mazaheri,1,*
    1. Department of Biology, School of Science, Payam Noor University of Esfahan, Isfahan, Iran


  • Introduction: Chronic inflammation is associated with carcinogenesis, especially in digestive organs. The mechanism of this effect, however, has only been partially focused on. This study was conducted with the aim of identifying genetic markers related to immunity and early prognostic pathways and prevention of Gastric cancer (GC).
  • Methods: This objective was achieved through the analysis of differentially expressed genes (DEGs) from two datasets obtained from the Gene Expression Omnibus (GEO). By doing so, we aimed to identify the hub genes associated with gastric adenocarcinoma that could serve as potential biomarkers and the most prominent pathways for early detection and management of GC. Two GEO datasets (GSE54129, and GSE79973), consisting of 21 normal and 33 GC samples, were analyzed using the Transcriptome Analysis Console (TAC) software. Functional enrichment analysis of DEGs was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes database (KEGG). Visualized PPI network analysis was performed by Cytoscape to further identify hub genes. Centrality parameters including degree, betweenness, and closeness were calculated to identify hub genes in the network using Gephi. Among the 100 selected hub genes, it was used to identify smaller communities that form groups of hub genes, called modules. Then the hub genes were imported to ENRICHR to find the most important pathways.
  • Results: A total of 1,495 common DEGs emerged among the datasets, focusing on significant GC-related pathways. six hub genes (IL6, FN1, MMP9, TGFB, COL1A1, and CD4) are associated with GC through PPI analysis. Based on multilevel systems biology analysis, hub genes in gastric adenocarcinoma showed participation in pathways such as AGE-RAGE signaling pathway in diabetic complications, focal adhesion, Proteoglycans in cancer, and other signaling pathways. Since targeting these genes may have multiple side effects, we decided to target the hub gene in a signaling pathway that specifically affects gastric cancer.
  • Conclusion: Our findings suggest that the identified hub genes, especially IL6, FN1, MMP9, TGFB, COL1A1, and CD4, play an important role in the inflammatory response in GC. This comprehensive analysis increases our understanding of the molecular mechanisms underlying GC development and may help identify potential therapeutic targets and prognostic markers for GC patients.
  • Keywords: gastric adenocarcinoma; bioinformatics; gene expression omnibus; inflammatory markers