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Feasibility of mcroRNAs as biomarkers for Barrett's Esophagus progression: a pilot cross-sectional, phase 2 biomarker study.

AbstractOBJECTIVES:
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.
AuthorsAjay Bansal, I H Lee, X Hong, V Anand, S C Mathur, S Gaddam, A Rastogi, S B Wani, N Gupta, M Visvanathan, P Sharma, L K Christenson
JournalThe American journal of gastroenterology (Am J Gastroenterol) Vol. 106 Issue 6 Pg. 1055-63 (Jun 2011) ISSN: 1572-0241 [Electronic] United States
PMID21407181 (Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Biomarkers
  • Genetic Markers
  • MicroRNAs
Topics
  • Adenocarcinoma (genetics, pathology)
  • Aged
  • Barrett Esophagus (genetics, pathology)
  • Biomarkers (analysis)
  • Biopsy, Needle
  • Cross-Over Studies
  • Disease Progression
  • Feasibility Studies
  • Female
  • Gene Expression Regulation
  • Genetic Markers
  • Humans
  • Immunohistochemistry
  • Linear Models
  • Male
  • MicroRNAs (analysis)
  • Microarray Analysis
  • Middle Aged
  • Pilot Projects
  • Precancerous Conditions (genetics, pathology)
  • Predictive Value of Tests
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Assessment

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