Background: Gastric carcinogenesis progresses from normal mucosa, atrophic/metaplastic gastritis, and dysplasia to adenocarcinoma. MicroRNAs (miRNAs) regulate DNA expression and have been implicated; however, their role is not fully established. Aims: The aim of this study was to characterize plasma and tissue expression of several miRNAs in gastric carcinogenesis stages. Methods: Single-center cross-sectional study in 64 patients: 19 controls (normal mucosa); 15 with extensive atrophic/metaplastic gastritis; and 30 with early gastric neoplasia (EGN). Seven miRNAs (miR-21, miR-146a, miR-181b, miR-370, miR-375, miR 181b, and miR-490) were quantified by real time-qPCR in peripheral blood and endoscopic biopsy samples. Results: We found a significant upregulation of miR-181b, miR-490, and miR-21 in the EGN mucosa (overexpression 2–14-times higher than controls). We observed a significant underexpression of miR-146a and miR-370 in atrophic/metaplastic gastritis (86 and 66% decrease, p = 0.008 and p = 0.001) and in EGN (89 and 62% reduction, p = 0.034 and p = 0.032) compared with controls. There were no differences between lesions and nonneoplastic mucosa and no dysregulation of plasma miRNAs. Conclusion: We found significant dysregulation of 5 miRNAs in gastric carcinogenesis, suggesting a tumor suppressor role for miR-146a and miR-370 and oncogenic potential for miR-21, miR-181, and miR-490. These changes happen diffusely in the gastric mucosa, suggesting a high-risk field defect, which may influence these patients’ surveillance.
Pathobiology

中文翻译：

---

原创文章：胃癌发生级联中的 MicroRNA 失调：我们能否预测其在个体化护理中的作用？

背景：胃癌的发生从正常黏膜、萎缩性/化生性胃炎和不典型增生发展为腺癌。MicroRNAs (miRNAs) 调节 DNA 表达并被牵连；但是，它们的作用尚未完全确立。目的：本研究的目的是表征几种 miRNA 在胃癌发生阶段的血浆和组织表达。方法：对 64 名患者进行单中心横断面研究：19 名对照（正常黏膜）；15 患有广泛的萎缩性/化生性胃炎；30 人患有早期胃肿瘤（EGN）。通过实时 qPCR 在外周血和内窥镜活检样本中定量 7 种 miRNA（miR-21、miR-146a、miR-181b、miR-370、miR-375、miR 181b 和 miR-490）。结果：我们发现 EGN 黏膜中 miR-181b、miR-490 和 miR-21 显着上调（过表达比对照高 2-14 倍）。我们观察到 miR-146a 和 miR-370 在萎缩性/化生性胃炎（分别减少 86% 和 66%，p = 0.008 和p = 0.001）和 EGN（减少 89% 和 62%，p = 0.034 和p = 0.032）中显着低表达) 与对照组相比。病变和非肿瘤性粘膜之间没有差异，血浆 miRNA 也没有失调。结论：我们发现 5 种 miRNA 在胃癌发生中的显着失调，表明 miR-146a 和 miR-370 具有肿瘤抑制作用，而 miR-21、miR-181 和 miR-490 具有致癌潜力。这些变化广泛发生在胃粘膜中，表明存在高风险的视野缺损，这可能会影响这些患者的监测。
病理学