揭示幽门螺杆菌感染与自身免疫性胃炎中的癌相关化生细胞

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

GASTROENTEROLOGY

影响因子:25.1

分区:医学1区 Top / 胃肠肝病学1区

发表日期:2025 Jan

作者: Stella G Hoft, Michelle Brennan, Javier A Carrero, Nicholas M Jackson, Challen A Pretorius, Tarin M Bigley, José B Sáenz, Richard J DiPaolo

DOI: 10.1053/j.gastro.2024.08.032

摘要

胃化生可能是慢性炎症的结果，并与胃癌发生风险增加相关。虽然幽门螺杆菌（Hp）感染和自身免疫性胃炎（AIG）都可诱导胃化生，但两者产生的化生细胞的潜在差异及其各自的癌变风险仍需进一步研究。利用小鼠模型和人类样本，我们详细分析了由Hp感染和AIG引起的化生的起源。通过组织病理学评估胃部病变和化生，结合单细胞转录组学在鼠模型和患者的活检标本中定义化生细胞的分子特征。免疫荧光确认了一种新定义的与癌症相关的化生标志物的表达。Hp感染和AIG引起的化生在组织学和转录特征上具有相似性。两种疾病中均观察到多种化生亚型，且在炎症背景下某些亚型的比例存在细微差异。值得注意的是，Hp感染未引起特定的化生细胞表型。两种疾病中都发现了一种类似不完全肠化生的化生亚型，其转录特征与胃癌相似，且表达癌相关标志物ANPEP/CD13。该癌样化生亚型的特征是表达癌相关的生物标志物ANPEP/CD13。研究发现，Hp感染和AIG均能引发多样的化生细胞类型。在两种疾病中，共同存在一种特异性表达ANPEP/CD13的癌相关化生细胞，表明这两种疾病均具有潜在的致癌性。这一发现为早期检测和风险分层提供了新的思路，特别是在慢性胃炎患者中。

Abstract

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.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.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.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.