Investigating CYP2C9 as a potential biomarker for gastric adenocarcinoma using bioinformatics analysis

Gastric cancer is a complex and an aggressive type of cancer within the stomach lining. Due to lack of specific symptoms and signs in early stages of gastric cancer, patients are still mostly diagnosed at the advanced stage with consequent poor outcome and poor survival rate. There is an urgency to identify novel biomarkers to predict and detect gastric cancer at the early stage. Cytochrome p450 genes (CYP450) are crucial players in phase 1- xenobiotic metabolism that metabolizes many xenobiotics and endogenous molecules. CYP450 play an important role in carcinogenesis, chemoprevention, and chemotherapy. However, connection between gastric cancer and CYP450 remain unclear. In this study, how changes in the expression level of the identified CYP450 polymorphism correlate with gastric cancer progression have been investigated. Comprehensive strategy which involves identification of differential expressed genes (DEGs), network analysis, enrichment analysis and survival analysis were implemented to elucidate and validate the correlation of cytochrome P450 genes as a potential biomarker for gastric cancer. A total of 168 DEGs were identified from GSE13911 which includes 59 upregulated genes and 109 downregulated genes. From the GEO2R analysis of GSE13911, four CYP2C9 (downregulated) were detected. Based on the PPI network constructed using the identified DEGs, 20 core genes were identified. The GO analysis results showed that the DEGs were significantly enriched in certain biological processes including potassium ion transport. The KEGG pathway enrichment analysis for downregulated genes were significantly enriched in gastric acid secretion, glycerolipid metabolism, retinol metabolism, metabolism of xenobiotics by cytochrome P450 and metabolic pathways. According to cBioPortal survival analysis high expression of CYP2C9 gene is associated with increased probability of overall survival (OS) and low expression of CYP2C9 gene is associated with reduced survival rate. Based on findings from this study, gastric cancer predispositions are not only due to changes in CYP2C9 gene expression, but it may be influenced by multiple genes. Low expression of CYP2C9 gene may be associated with increased risk of developing gastric cancer. Identifying individuals with low expression of CYP2C9 could help improve the survival rate of patient with high-risk gastric cancer associated with low expression of CYP2C9.Ph.D.Includes bibliographical reference