Dissecting the Single-Cell Transcriptome Network Underlying Gastric Premalignant Lesions and Early Gastric Cancer

摘要

Intestinal-type gastric cancer is preceded by premalignantlesions, including chronic atrophic gastritisand intestinal metaplasia. In this study, we constructeda single-cell atlas for 32,332 high-qualitycells from gastric antral mucosa biopsies of patientsspanning a cascade of gastric premalignant lesionsand early gastric cancer (EGC) using single-cellRNA sequencing. We then constructed a single-cellnetwork underlying cellular and molecular characteristicsof gastric epithelial cells across different lesions.We found that gland mucous cells tended toacquire an intestinal-like stem cell phenotype duringmetaplasia, and we identified OR51E1 as a markerfor unique endocrine cells in the early-malignantlesion. We also found that HES6 might mark thepre-goblet cell cluster, potentially aiding identificationof metaplasia at the early stage. Finally, we identifieda panel of EGC-specific signatures, with clinicalimplications for the precise diagnosis of EGC. Ourstudy offers unparalleled insights into the humangastric cellulome in premalignant and early-malignantlesions.