Abstract

Gastric intestinal metaplasia (GIM) is a precancerous lesion closely associated with gastric cancer (GC) risk. A systematic characterization of the molecular profiles across distinct cell types during GIM progression is crucial for devising new intervention strategies and enabling early prevention for GC. This study integrates single-cell transcriptomics and proteomics data from gastric tissues of patients with mild chronic non-atrophic gastritis (CNAG) and moderate-to-severe GIM. We identified differentially expressed genes (DEGs) and proteins (DEPs) that show consistent changes at both transcriptional and protein levels across epithelial, stromal, and immune cells. Notably, most proteins were downregulated in GIM tissues, potentially linked to reduced expression of RNA splicing-related genes. Epithelial cells in GIM lesions exhibited intestinal-type subpopulations, including goblet and enterocytes, likely originating from gastric isthmus stem cells. Despite overall protein downregulation, the ubiquitin-like protein NEDD8 was markedly upregulated in metaplastic tissues, especially in H. pylori-positive tissues. Pathways involved in cytoskeleton maintenance, extracellular matrix stability, and cell adhesion were downregulated, while several macrophage-expressed DEGs/DEPs (e.g., BST2, CYBB, ITGB2) were elevated. This work delineates dynamic transcriptional and translational alterations during the progression from mild gastritis to GIM. It implies that chronic inflammatory injury causes suppress protein synthesis, further driving metaplastic transformation early gastric precancerous lesions.