Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.
Gastroenterology Unit, Azienda Ospedale Università -Padova, Padua, Italy.
Front Immunol. 2022 Jul 22;13:930989. doi: 10.3389/fimmu.2022.930989. eCollection 2022.
MicroRNAs (miRNAs) have been proposed as diagnostic markers, biomarkers of neoplastic progression, and possible therapeutic targets in several immune-mediated diseases. We aimed to analyze the expression profile of selected miRNAs (miR21, miR142, miR223, miR155) in patients with autoimmune atrophic gastritis (AAG), patients with non-autoimmune multifocal atrophic gastritis (MAG), and healthy control subjects (HC).
A total of 103 patients with AAG were consecutively recruited for this study among those attending our gastroenterology outpatient clinic. Participating patients were divided into two groups: primary, not Helicobacter pylori (HP)-associated related AAG (n=57, P-AAG) and HP-associated AAG (n=46, HP-AAG); this subgroup included HP-positive patients, patients with previously reported HP infection, and patients harboring antral atrophy, considered as a stigma of HP infection. We also included 20 sex-age-matched MAG patients and 10 HC. Upper endoscopy with gastric biopsies were performed on each AAG and MAG patient. Circulating levels of miR21-5p, miR142-3p, miR223-3p, and miR155-5p were measured by RT-PCR in all groups.
MiR-21 was over-expressed in P-AAG (p=0.02), HP-AAG (p = 0.04), and MAG (p=0.03) compared with HC. By contrast, miR-142 was more expressed in HC than in HP-AAG (p=0.04) and MAG (p=0.03). MiR-155 showed no significant differences among the four subgroups, while, unexpectedly, miR-223 was overexpressed in HC compared to P-AAG (p=0.01), HP-AAG (p=0.003), and MAG (p<0.001), and was higher in P-AAG than in MAG (p=0.05).
MiR-21 was over-expressed in patients with gastric precancerous conditions irrespective of etiology, while in the same subgroups miR-142 and miR-223 were under-expressed compared to healthy controls. Controlling miRNAs up- or downregulation could lead to a breakthrough in treating chronic autoimmune diseases and potentially interfere with the progression to cancer.
MicroRNAs（miRNAs）已被提出作为几种免疫介导疾病的诊断标志物、肿瘤进展的生物标志物和可能的治疗靶点。我们旨在分析选定的 miRNAs（miR21、miR142、miR223、miR155）在自身免疫性萎缩性胃炎（AAG）患者、非自身免疫性多灶性萎缩性胃炎（MAG）患者和健康对照者（HC）中的表达谱。
本研究共纳入 103 名连续就诊于我院消化科门诊的 AAG 患者。纳入的患者分为两组：原发性、非幽门螺杆菌（HP）相关的 AAG（n=57，P-AAG）和 HP 相关的 AAG（n=46，HP-AAG）；该亚组包括 HP 阳性患者、有既往报道的 HP 感染患者和有胃窦萎缩的患者，胃窦萎缩被认为是 HP 感染的标志。我们还纳入了 20 名性别年龄匹配的 MAG 患者和 10 名 HC。对每位 AAG 和 MAG 患者进行上消化道内镜检查和胃活检。采用 RT-PCR 法检测所有组中 miR21-5p、miR142-3p、miR223-3p 和 miR155-5p 的循环水平。
与 HC 相比，miR-21 在 P-AAG（p=0.02）、HP-AAG（p=0.04）和 MAG（p=0.03）中表达升高。相比之下，miR-142 在 HC 中表达高于 HP-AAG（p=0.04）和 MAG（p=0.03）。miR-155 在四组之间无显著差异，而 miR-223 出乎意料地在 HC 中表达高于 P-AAG（p=0.01）、HP-AAG（p=0.003）和 MAG（p<0.001），且高于 P-AAG 高于 MAG（p=0.05）。
miR-21 在胃癌前病变患者中表达升高，无论病因如何，而在相同的亚组中，miR-142 和 miR-223 的表达低于健康对照组。控制 miRNAs 的上调或下调可能会在治疗慢性自身免疫性疾病方面取得突破，并可能干扰癌症的进展。
