World Gastroenterology Organisation

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Single-cell transcriptomic profiling uncovers cellular complexity and microenvironment in gastric tumorigenesis associated with Helicobacter pylori

Review by Prof. Zikai Wang (China)

Study Summary 

This study revealed cellular heterogeneity and alterations in tissue ecology throughout the progression of gastric carcinoma through Single-cell RNA sequencing (scRNA-seq). The study also discovered a specific epithelial cell population enterocyte from precancerous lesion gastrointestinal metaplasia, and HNF4G was predicted as its specific transcription factor. In addition, the differentia expressed genes (DEGs) in epithelial, fibroblasts and myeloid cells associated with H. pylori infection have been identified. Meanwhile, the study found that H. pylori-positive specimens exhibited enriched cell-cell communication with significantly active TNF, SPP1, and THY1 signaling networks. 

Commentary 

This study conducted a comprehensive single-cell atlas throughout the progression of gastric carcinoma. Immunofluorescence staining, immunohistochemistry, and qRT-PCR revealed the heterogeneity and alterations during the progression of gastric cancer. The unique expression profiles of tumor-like epithelial cell subset (EPC), inflammatory cancer-associated fibroblasts (iCAFs), and Tumor-associated macrophage (TAM) in gastric cancer were discovered. The study also found that epithelial subset enterocytes in the precancerous lesion are significantly enriched in lipid metabolism genes, and HNF4G might be closely related to intestinal metaplasia. In addition, the study identified that Hp-positive groups exhibited more active intercellular communication, such as TNF, THY1, and SPP1 signaling networks. In summary, this study uncovered the molecular mechanism of gastric cancer, providing a new idea for the prevention and treatment of gastric cancer.

Citation

Li N, Chen S, Xu X, et al. Single-cell transcriptomic profiling uncovers cellular complexity and microenvironment in gastric tumorigenesis associated with Helicobacter pylori. J Adv Res. Published online October 15, 2024. doi:10.1016/j.jare.2024.10.012

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