ArticleFrontiers in immunology2026
Integrated single-cell and spatial transcriptomics reveal the differentiation drivers of gastric epithelial lineage progression.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed.
- Review
- Molecular Mechanisms and Biomarkers Driving the Transition From Chronic Atrophic Gastritis to Gastric Cancer.Clinical Medicine Insights. Oncology · 2026Review
- Patient-derived organoids in gastric cancer: bridging the tumor microenvironment to functional precision oncology.Frontiers in bioengineering and biotechnology · 2026Review
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Authors and funding
11 authors.
Funding
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Abstract
Gastric cancer (GC) develops through a sequence from chronic gastritis to intestinal metaplasia (IM) and carcinoma, with Helicobacter pylori (HP) as a key driver; however, the molecular mediators linking inflammation to malignant transformation remain unclear. We integrated single-cell RNA sequencing and spatial transcriptomics of gastric mucosal samples from atrophic gastritis, IM, and GC, including HP positive (+) and HP negative (-) cases, to map cellular heterogeneity, differentiation trajectories, and pathway activities. Our analyses revealed that IM epithelium represents a transitional state between normal and malignant epithelial lineages, characterized by enhanced WNT signaling that promotes neoplastic progression, whereas H. pylori-associated inflammation activates NF-κB signaling. Across analysis, UPP1 was consistently upregulated in malignant and H. pylori-positive epithelium, increasing along pseudotime toward cancer-like states. Spatial mapping and organoid experiments confirmed that UPP1-high cells had higher intestinal differentiation scores, while UPP1 knockout promoted IM-like morphology in WNT-depleted cultures. Clinically, UPP1 was elevated in GC versus normal tissues, correlated with advanced TNM stage, predicted poor survival, and was higher in HP
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Registered trials
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