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Predictive Value of MicroRNAs in the Progression of Barrett Esophagus to Adenocarcinoma in a Long-Term Follow-up Study

Revilla-Nuin, Beatriz PhD*,§; Parrilla, Pascual MD, PhD*,§; Lozano, Juan Jose PhD§; de Haro, Luisa F. Martínez MD, PhD; Ortiz, Angeles MD, PhD*,§; Martínez, Carlos PhD*,§; Munitiz, Vicente MD, PhD*,§; de Angulo, David Ruiz MD*,§; Bermejo, Juan MD†,§; Molina, Joaquin MD‡,§; Cayuela, María L. PhD*,¶; Yélamos, José PhD§,‖,¶

Annals of Surgery:
doi: 10.1097/SLA.0b013e31826ddba6
Original Articles
Abstract

Objective: The aim of this study is to identify a set of microRNAs (miRNAs) as prognostic molecular biomarkers for the progression of Barrett esophagus (BE) to esophageal adenocarcinoma (EAC) to rationalize the surveillance programs in patients with BE.

Background: Histological dysplasia is currently used as the main biomarker to identify the BE patients at high risk for developing EAC. Although miRNA expression profiles in BE and EAC have been reported, it has not been established which set of miRNAs could constitute a robust diagnostic test to predict the progression of BE to EAC.

Methods: miRNAs associated with progression of BE to EAC were identified using miRNA sequencing analysis. Further validation by quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed in 2 groups of BE patients who either developed or did not develop adenocarcinoma after at least 5 years of follow-up.

Results: Twenty-three miRNAs were identified by miRNA sequencing analysis in the carcinogenesis process associated with BE. qRT-PCR analysis using independent tissue samples confirmed differential expression for 19 of them (miR-let-7c, 7, 146a, 149, 153, 192, 192*, 194, 194*, 196a, 196b, 200a, 203, 205, 215, 424, 625, 625*, and 944). However, only miR-192, 194, 196a, and 196b showed a significantly higher expression in BE samples from patients with progression to EAC compared with those who did not progress to EAC.

Conclusions: These findings suggest that the expression pattern of a modest number of miRNAs in metaplasia biopsies could identify the BE patients at high risk for developing EAC. Therefore, it has potential use for the control and treatment of this malignancy.

In Brief

MicroRNAs (miRNAs) are an ideal biomarker for cancer. We report that a modest number of miRNAs in metaplasia biopsies could identify the patients with Barrett esophagus at high risk for developing esophageal adenocarcinoma. Therefore, it has potential use for the control and treatment of this malignancy.

Author Information

*Department of Surgery

Department of Pathology

Endoscopy Unit, University Hospital Virgen de la Arrixaca, Murcia, Spain

§CIBERehd, Barcelona, Spain

Department of Immunology, Cancer Research Program, IMIM-Hospital del Mar, Barcelona, Spain

Equal contribution by the authors.

Reprints: Pascual Parrilla, MD, PhD, Department of Surgery, CIBERehd, Murcia, Spain. E-mail: pascual.parrilla2@carm.es; Maria L. Cayuela, PhD, Department of Surgery, Department of Virgen de la Arrixaca, El Palmar, 30120-Murcia, Spain. E-mail: marial.cayuela@carm.es.

Disclosure: This study has been supported by grants from the Fondo de Investigación Sanitaria (FIS) (PI09/1808), Fundación Mutua Madrileña, and Fundación Séneca (08823/PI/08). The authors declare that they have nothing to disclose.

© 2013 by Lippincott Williams & Wilkins.