在幽门螺杆菌感染和自身免疫性胃炎中揭示与癌症相关的化生细胞
Unveiling Cancer-Related Metaplastic Cells in Both Helicobacter pylori Infection and Autoimmune Gastritis
影响因子:25.10000
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
摘要
由于慢性炎症，可能会出现胃化生，并且与胃癌发展的风险增加有关。尽管幽门螺杆菌（HP）感染和自身免疫性胃炎（AIG）都诱导胃代理，但导致的化生细胞及其各自的癌症风险可能会进一步研究。使用小鼠模型和人类参与者，我们从HP INFECTION和AIG中审查了Mectaplasia。通过组织病理学评估检查胃病理学和化生。在HP感染和AIG的鼠模型以及HP感染和AIG患者的人类活检标本中，使用单细胞转录组学定义了化生细胞的分子特征。通过免疫荧光证实了新定义的与癌症相关的化生生物标志物的表达。HP感染中的甲状腺素和AIG表现出可比的组织病理学和转录特征。在两种疾病环境中都鉴定出不同的化生亚型，在炎症环境之间某些亚型的患病率上有细微的差异。值得注意的是，HP感染不会驱动独特的化生细胞表型。在两种疾病中都鉴定出一种类似于不完全的肠上皮氏菌和与胃癌共享的转录特征的化生亚型。这种类似癌症的化生亚型的特征是表达与癌症相关的生物标志物ANPEP/CD13。在HP和AIG诱导的胃炎中都存在与癌症相关的化生细胞唯一表达ANPEP/CD13的鉴定，表明两种疾病的致癌能力。该发现可以指导慢性胃炎患者的早期检测和风险分层。
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.