© 2011 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY INTRODUCTION Esophageal adenocarcinoma (EAC) is the fastest growing inci- dence cancer in North America (1). Te presence of Barrett’s esophagus (BE) increases the risk of EAC by 30- to 40-fold (2). To identify the BE patients at high risk for progression to adenocar- cinoma, presence of histologic dysplasia is currently used as the main biomarker, as adenocarcinoma in BE is thought to evolve through the stages of non-dysplastic intestinal metaplasia (IM), low-grade dysplasia, high-grade dysplasia (HGD), and fnally cancer. However, dysplasia sufers from poor inter-observer agreement (3), sampling error, and limited positive predictive value (2). Additionally, in a large multicenter cohort study, as Feasibility of MicroRNAs as Biomarkers for Barrett’ s Esophagus Progression: A Pilot Cross-Sectional, Phase 2 Biomarker Study Ajay Bansal, MD 1,2 , I.H. Lee, PhD 3,6 , X . Hong, MD 4,6 , V. Anand, MS 3 , S.C. Mathur, MD 5 , S. Gaddam, MD 1 , A. Rastogi, MD 1,2 , S.B. Wani, MD 1 , N. Gupta, MD 1 , M. Visvanathan, PhD 3 , P. Sharma, MD 1,2 and L.K. Christenson, PhD 4 OBJECTIVES: Risk stratification of Barrett’ s esophagus (BE) using biomarkers remains an important goal. We evaluated feasibility and clinical accuracy of novel microRNA (miRNA) biomarkers for prediction of BE dysplasia. METHODS: Paired fresh-frozen and hematoxylin/eosin specimens from a prospective tissue repository where only biopsies with the lesion of interest (i.e., intestinal metaplasia (IM) or high-grade dysplasia (HGD)/ esophageal adenocarcinoma (EAC)) occupying > 50% of biopsy area were included. Tissue miRNA expression was determined by microarrays and validated by quantitative reverse transcription-PCR (qRT-PCR). Three groups were compared—group A, IM tissues from BE patients without dysplasia; group B, IM tissues from group C patients; and group C, dysplastic tissues from BE patients with HGD/EAC. RESULTS: Overall, 22 BE patients, 11 with and without dysplasia (mean age 64±8.2 and 63±11.6 years, respectively, all Caucasian males) were evaluated. Nine miRNAs were identified by high-throughout analysis (miR-15b, -21, -192, -205, 486-5p, -584, -1246, let-7a, and -7d) and qRT-PCR confirmed expression of miR-15b, -21, 486-5p, and let-7a. Two of 4 miRNAs (miR-145 and -203, but not -196a and -375) previously described in BE patients also exhibited differential expression. Sensi- tivity and specificity of miRNAs for HGD/EAC were miR-15b: 87 and 80%, miR-21: 93 and 70%, miR-203: 87 and 90%, miR-486-5p: 82 and 55%, and miR-let-7a: 88 and 70%. MiRNA-15b, -21, and -203 exhibited field effects (i.e., groups A and B tissues while histologically similar yet exhibited different miRNA expression). CONCLUSIONS: This pilot study demonstrates feasibility of miRNAs to discriminate BE patients with and without dys- plasia with reasonable clinical accuracy. However, the specific miRNAs need to be evaluated further in future prospective trials. SUPPLEMENTARY MATERIAL is linked to the online version of the paper at http://www.nature.com/ajg Am J Gastroenterol 2011; 106:1055–1063; doi:10.1038/ajg.2011.37; published online 15 March 2011 1 Division of Gastroenterology and Hepatology, Veterans Affairs Medical Center and University of Kansas Medical Center , Kansas City , Kansas, USA; 2 Kansas Cancer Institute, University of Kansas Medical Center, Kansas City , Kansas, USA; 3 Bioinformatics Core Facility, University of Kansas, Lawrence, Kansas, USA; 4 Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Missouri, USA; 5 Department of Pathology, Veterans Affairs Medical Center and University of Kansas Medical Center, Kansas City, Missouri, USA; 6 These authors contributed equally to this work. Correspondence: Ajay Bansal, MD, Department of Gastroenterology, Veterans Affairs Medical Center, University of Kansas School of Medicine, 4801 E. Linwood Blvd., Kansas City , Missouri, USA. E-mail: abansal@kumc.edu Received 30 September 2010; accepted 5 January 2011 ESOPHAGUS 1055 1055 ORIGINAL CONTRIBUTIONS nature publishing group