UNVEILING CANCER-RELATED METAPLASTIC CELLS IN BOTH HELICOBACTER PYLORI INFECTION AND AUTOIMMUNE GASTRITIS

Background and AimsGastric metaplasia may arise as a consequence of chronic inflammation and is associated with an increased risk of gastric cancer development. While Helicobacter pylori (Hp) infection and autoimmune gastritis (AIG) both induce gastric metaplasia, possible distinctions in resulting metaplastic cells and their respective cancer risks requires further investigation.MethodsEmploying both mouse models and human subjects, we scrutinized the metaplasia originating from Hp infection and AIG. Gastric pathology and metaplasia were examined through histopathologic assessment. Molecular features of metaplastic cells were defined using single-cell transcriptomics in murine models of Hp infection and AIG, as well as in human biopsies from patients with Hp infection and AIG. Expression of a newly defined cancer-related metaplastic biomarker was confirmed through immunofluorescence.ResultsMetaplasia in Hp infection and AIG displayed comparable histopathological and transcriptional features. Diverse metaplastic subtypes were identified across both disease settings, with subtle differences in the prevalence of certain subtypes between inflammatory contexts. Notably, Hp infection did not drive a unique metaplastic cell phenotype. One metaplastic subtype, which resembled incomplete intestinal metaplasia and shared transcriptional features with gastric cancer was identified in both diseases. This cancer-like metaplastic subtype was characterized by expression of the cancer-associated biomarker ANPEP/CD13.ConclusionBoth Hp infection and AIG trigger a diverse array of metaplastic cell types. Identification of a cancer-related metaplastic cell uniquely expressing ANPEP/CD13, present in both Hp- and AIG-induced gastritis, indicates the carcinogenic capacity of both diseases. This discovery can guide early detection and risk stratification for patients with chronic gastritis.Graphical abstract