Pivot gene enrichment analysis of Streptococcus pyogenes specific hyaluronic acid mediated disease prognosis on gastric cancer: Based on bioinformatics study.

BACKGROUND: Gut ecosystem is maintained by immune regulation through intestinal microbiota that leads to inflammatory diseases such as Gastric Cancer. Hyaluronic acid is derived from gut microorganism Streptococcus pyogenes which directly controls the up and down regulation of potential gene sets that helps to promote or inhibit gastric cancer.

METHODS: GEO database is used to observe potential hub genes related to hyaluronic acid mediated gastric cancer. Gene expression analysis and PPI network analysis are implicated through EMBL-EBI and STRING database under DAVID software respectively. Gene interactions are studied by Reactome data source and gene networking is identified through GeneMANIA online server. BIOVENN is used for producing Venn diagram and GSEA is followed for generation of Heat Map. Identification of Microbial Signal Transduction through MiST website, regulons and transcription factors analysis through RegPrecise and MetaCyc web source is incorporated for biosynthetic pathway analysis. TCGA is incorporated for studying cancer genomics and gene interaction pathways. KEGG Pathway enrichment is done through ShinyGO resource. KM-Survival Plots is depicted through CybersortX. Genome expressional analysis is done by GEPIA web portal. Resistomes and Variants isolation and bi-product of Streptococcus pyogenes MGAS are implicated through CARD and BV-BRC database. Ligand-Drug Analysis and TCGA Drug Response and Survival Analysis are incorporated through MCULE and GEPIA 3 web source.

RESULTS: Differential Expression Analysis has identified up-regulated and down-regulated genes related to HMMR gene. Venn Analysis interpreted 3 co-expressed genes within HMMR, IL1B and HAS3 genes. Global Cancer Heat Map of HMMR gene has shown high expression level of intensity value 0.50204 to lowest value -0.58367. Cellular response related to HMMR gene is responsible for programmed cell death due to inactivation of Cyclin B (Cdk1) complex mediated by Chk1/Chk2 (Cds1). Streptococcus pyogenes mediated biological pathways, transcription factors, regulons and genomic analysis of HMMR protein are also identified. KEGG Enrichment Analysis shows NF-kB Signaling pathway with Hyaluronic Acid mediated network gene set. KM-Survival Analysis is depicted through Hazard Ratio (HR) and p-value identification. Drug-Target Docking Analysis of ligand molecule Hyaluronic Acid and drugs 5-Fluorouracil and Epirubicin and TCGA Drug Survival Analysis and Response are implicated for therapeutic interventions.