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. 2025 Jan;168(1):53-67.
doi: 10.1053/j.gastro.2024.08.032. Epub 2024 Sep 3.

Unveiling Cancer-Related Metaplastic Cells in Both Helicobacter pylori Infection and Autoimmune Gastritis

Stella G Hoft  1 , Michelle Brennan  2 , Javier A Carrero  1 , Nicholas M Jackson  1 , Challen A Pretorius  1 , Tarin M Bigley  3 , José B Sáenz  4 , Richard J DiPaolo  5
Affiliations

Unveiling Cancer-Related Metaplastic Cells in Both Helicobacter pylori Infection and Autoimmune Gastritis

Stella G Hoft et al. Gastroenterology. 2025 Jan.

Abstract

Background & aims: Gastric metaplasia may arise as a consequence of chronic inflammation and is associated with an increased risk of gastric cancer development. Although 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.

Methods: Using both mouse models and human participants, 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 biopsy specimens from patients with Hp infection and AIG. Expression of a newly defined cancer-related metaplastic biomarker was confirmed through immunofluorescence.

Results: Metaplasia in Hp infection and AIG displayed comparable histopathologic 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.

Conclusion: Both 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.

Keywords: Autoimmune Gastritis; Gastric Cancer; Gastric Inflammation; Gastric Metaplasia; Helicobacter pylori Infection.

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Conflict of interest statement

CONFLICT OF INTEREST

There are no conflicts of interest to disclose.

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