Integrated single-cell and spatial transcriptomics reveal the differentiation drivers of gastric epithelial lineage progression - PubMed
6 hours ago
- #Helicobacter pylori
- #UPP1
- #Gastric cancer
- Gastric cancer (GC) develops through stages from chronic gastritis to intestinal metaplasia (IM) and carcinoma, with Helicobacter pylori (HP) as a key driver.
- Integrated single-cell RNA sequencing and spatial transcriptomics revealed IM epithelium as a transitional state between normal and malignant epithelial lineages, characterized by enhanced WNT signaling.
- H. pylori-associated inflammation activates NF-κB signaling, while UPP1 was consistently upregulated in malignant and H. pylori-positive epithelium.
- UPP1-high cells showed higher intestinal differentiation scores, and UPP1 knockout promoted IM-like morphology in WNT-depleted cultures.
- Clinically, UPP1 was elevated in GC, correlated with advanced TNM stage, predicted poor survival, and was higher in HP+ tissues.
- UPP1 knockdown in GC cell lines reduced clonogenicity and migration, identifying it as a key regulator of epithelial reprogramming and IM.
- UPP1 links H. pylori-driven inflammation with WNT-mediated differentiation and has potential as a prognostic biomarker and therapeutic target in GC.