ABSTRACT:
The progression from chronic Helicobacter pylori–associated gastritis to intestinal metaplasia represents a critical precancerous stage in gastric carcinogenesis. However, the transcriptomic alterations underlying this transition remain poorly characterized. To identify transcriptomic alterations and key biological pathways involved in the progression from Helicobacter pylori–associated gastritis to intestinal metaplasia. Publicly available gastric mucosal gene expression datasets were retrieved from samples of normal gastric mucosa, H. pylori–positive gastritis, and intestinal metaplasia. Differential gene expression and pathway enrichment analyses were performed to identify molecular changes associated with disease progression. Key regulatory networks were explored using gene set enrichment and protein–protein interaction analyses. Comparative transcriptomic analysis demonstrated a stepwise molecular shift from gastritis to intestinal metaplasia. H. pylori–positive gastritis was characterized by strong activation of inflammatory and innate immune pathways, including toll-like receptor signaling and cytokine–cytokine receptor interactions. Progression to intestinal metaplasia was marked by significant upregulation of epithelial differentiation, cell cycle dysregulation, and DNA damage response pathways. Notably, genes involved in Wnt/β-catenin signaling, epithelial–mesenchymal transition, and oxidative stress were consistently enriched in intestinal metaplasia samples. Network analysis identified several hub genes implicated in early malignant transformation and mucosal remodeling. These transcriptomic changes suggest a biological shift from inflammation-dominant responses toward proliferative and premalignant signaling. The transition from H. pylori–associated gastritis to intestinal metaplasia is driven by distinct and progressive transcriptomic reprogramming. Identification of early carcinogenic pathways provides potential molecular targets for risk stratification, surveillance, and early intervention in patients with chronic H. pylori infection.​​​