title: Feasibility of mcroRNAs as biomarkers for Barrett's Esophagus progression: a pilot cross-sectional, phase 2 biomarker study.
abstract: OBJECTIVE
  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. Sensitivity 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 dysplasia with reasonable clinical accuracy. However, the specific miRNAs need to be evaluated further in future prospective trials.
authors.affiliation: Division of Gastroenterology and Hepatology, Veterans Affairs Medical Center and University of Kansas Medical Center, Kansas City, Kansas, USA. abansal@kumc.edu
authors.forename: Ajay
authors.initials: A
authors.lastname: Bansal
authors.forename: I H
authors.initials: IH
authors.lastname: Lee
authors.forename: X
authors.initials: X
authors.lastname: Hong
authors.forename: V
authors.initials: V
authors.lastname: Anand
authors.forename: S C
authors.initials: SC
authors.lastname: Mathur
authors.forename: S
authors.initials: S
authors.lastname: Gaddam
authors.forename: A
authors.initials: A
authors.lastname: Rastogi
authors.forename: S B
authors.initials: SB
authors.lastname: Wani
authors.forename: N
authors.initials: N
authors.lastname: Gupta
authors.forename: M
authors.initials: M
authors.lastname: Visvanathan
authors.forename: P
authors.initials: P
authors.lastname: Sharma
authors.forename: L K
authors.initials: LK
authors.lastname: Christenson
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000368:Aged; D001471:Barrett Esophagus / Q000235:genetics* / Q000473:pathology*; D015415:Biomarkers / Q000032:analysis; D001707:Biopsy, Needle; D018592:Cross-Over Studies; D018450:Disease Progression; D005240:Feasibility Studies; D005260:Female; D005786:Gene Expression Regulation; D005819:Genetic Markers; D006801:Humans; D007150:Immunohistochemistry; D016014:Linear Models; D008297:Male; D035683:MicroRNAs / Q000032:analysis*; D046228:Microarray Analysis; D008875:Middle Aged; D010865:Pilot Projects; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology*; D011237:Predictive Value of Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment
chemical_list: D015415:Biomarkers; D005819:Genetic Markers; D035683:MicroRNAs