Single-cell transcriptomic profiling uncovers cellular complexity and microenvironment in gastric tumorigenesis associated with Helicobacter pylori
Helicobacter pylori (H. pylori) infection is a key initiating factor in the Correa cascade of gastric carcinogenesis, but the comprehensive understanding of the pathogenic mechanisms underlying H. pylori-induced GC remains elusive. Here, we generated a single-cell atlas of gastric tumorigenesis comprising 18 specimens of gastritis, intestinal metaplasia and gastric cancer (GC) with or without H. pylori infection.  We identified 48 distinct cell subpopulations including novel rare subtypes, and revealed the influence of H. pylori infection on cellular heterogeneity across neoplastic lesions. Overall design: A total of 18 patients pathologically diagnosed with gastric lesions at The First Affiliated Hospital of Nanchang University, including 6 of GS, 6 of IM, and 6 of GC, were enrolled in this study. The specimens of GS and IM were obtained during endoscopy, and the gastric carcinoma specimens were obtained from surgical samples without adjuvant therapy. The patients with gastric mucosal lesions were then divided into two groups according to H. pylori status. The sections with H&E staining were reviewed by senior pathologists. Status of H. pylori infection for these clinical specimens was determined with 13C-urea breath test (UBT), immunohistochemistry (IHC) and immunofluorescence (IF) staining. Additionally, formalin-fixed paraffin-embedded (FFPE) specimens including GS, IM and GC were collected from 120 patients for experimental validation. The clinical characteristics of patients were summarized in Table S1. The study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Nanchang University under protocol number of (2023) CDYFYYLK (01-009). All tissue samples were obtained under informed consent.