Original Article: MicroRNA Dysregulation in the Gastric Carcinogenesis Cascade: Can We Anticipate Its Role in Individualized Care?

Abstract

<b><i>Background:</i></b> 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. <b><i>Aims:</i></b> The aim of this study was to characterize plasma and tissue expression of several miRNAs in gastric carcinogenesis stages. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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, <i>p</i> = 0.008 and <i>p</i> = 0.001) and in EGN (89 and 62% reduction, <i>p</i> = 0.034 and <i>p</i> = 0.032) compared with controls. There were no differences between lesions and nonneoplastic mucosa and no dysregulation of plasma miRNAs. <b><i>Conclusion:</i></b> 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.