揭示幽门螺杆菌感染和自身免疫性胃炎中与癌症相关的化生细胞。
Unveiling Cancer-Related Metaplastic Cells in Both Helicobacter pylori Infection and Autoimmune Gastritis.
发表日期:2024 Sep 03
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
来源:
GASTROENTEROLOGY
摘要:
胃化生可能是慢性炎症的结果,并且与胃癌发展风险增加相关。尽管幽门螺杆菌 (Hp) 感染和自身免疫性胃炎 (AIG) 都会诱发胃化生,但所产生的化生细胞及其各自的癌症风险可能存在的差异需要进一步研究。使用小鼠模型和人类参与者,我们仔细检查了源自 Hp 感染的化生,并研究了胃化生。美国国际集团。通过组织病理学评估检查胃病理学和化生。利用 Hp 感染和 AIG 的小鼠模型以及 Hp 感染和 AIG 患者的人体活检标本中的单细胞转录组学来定义化生细胞的分子特征。通过免疫荧光证实了一种新定义的癌症相关化生生物标志物的表达。Hp 感染和 AIG 中的化生表现出相似的组织病理学和转录特征。在两种疾病环境中均发现了多种化生亚型,并且炎症背景下某些亚型的患病率存在细微差异。值得注意的是,Hp 感染并没有驱动独特的化生细胞表型。在这两种疾病中都发现了一种化生亚型,类似于不完全肠化生,并且与胃癌具有相同的转录特征。这种癌症样化生亚型的特征是表达癌症相关生物标志物丙氨酰氨基肽酶 N/CD13。Hp 感染和 AIG 都会引发多种化生细胞类型。鉴定出独特表达丙氨酰氨基肽酶 N/CD13 的癌症相关化生细胞(存在于 Hp 和 AIG 诱导的胃炎中)表明了这两种疾病的致癌能力。这一发现可以指导慢性胃炎患者的早期检测和风险分层。版权所有 © 2024 AGA Institute。由爱思唯尔公司出版。保留所有权利。
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 alanyl aminopeptidase N/CD13.Both Hp infection and AIG trigger a diverse array of metaplastic cell types. Identification of a cancer-related metaplastic cell uniquely expressing alanyl aminopeptidase N/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.Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.