Integrated transcriptomics and molecular docking identify hub genes and statin regulators in Helicobacter pylori-associated gastric mucosal pathogenesis.

BACKGROUND

Helicobacter pylori (H. pylori), a spiral Gram-negative bacterium colonizing gastric mucosa, damages epithelial cells, driving chronic gastritis, peptic ulcers, and gastric cancer. Mechanisms of its malignant transformation remain unclear.

METHODS

We identified differentially expressed genes (DEGs) and hub genes, pathway enrichment analysis, transcription factors (TFs), small-molecule drug and molecular docking prediction using gastric epithelial cells (GECs) infected with H. pylori strain 26695 and clinical sample datasets.

RESULTS

H. pylori infection of GECs, multiple signaling pathways were activated, including the p53, MAPK, TNF, IL-17, PI3K-Akt and NF-κB signaling, DNA replication, Apoptosis, Cell cycle, Necroptosis. A total of 107 co-expressed DEGs were identified in vitro and in vivo. Using Cytoscape, 20 hub genes were prioritized: TNF, CXCL8, NFKBIA, IRF1, ICAM1, TNFAIP3, BIRC3, CXCL1, ITGAM, RELB, CXCL2, CCL20, NFKB2, EGR1, CDKN1A, IRAK2, JAK1, NFKBIE, TRAF1, and JUNB. These hub genes were enriched in NF-κB, TNF and IL-17 signaling, and responses to bacterial pathogens or lipopolysaccharide. Further analysis identified 9 upregulated TFs: VDR, SPI1, ETS2, STAT1, E2F1, PML, ETS1, BRCA1, MYC, and 4 downregulated TFs: ING4, CEBPD, HSF1, JUN. To explore potential therapeutic interventions, we performed small-molecule drug prediction and molecular docking for hub genes revealed: Simvastatin: Linked to CCL20, NFKBIA, and ICAM1. Atorvastatin: Associated with CDKN1A, ICAM1, and TNF. TPCA-1: Targeting JAK1.

CONCLUSION

These findings provide a theoretical foundation for further investigation into the molecular mechanisms underlying H. pylori-related diseases.