title: MicroRNA Profiles of Barrett's Esophagus and Esophageal Adenocarcinoma: Differences in Glandular Non-native Epithelium.
abstract: BACKGROUND
  The tissue specificity and robustness of miRNAs may aid risk prediction in individuals diagnosed with Barrett's esophagus. As an initial step, we assessed whether miRNAs can positively distinguish esophageal adenocarcinoma from the precursor metaplasia Barrett's esophagus.
  
  
  METHODS
  In a case-control study of 150 esophageal adenocarcinomas frequency matched to 148 Barrett's esophagus cases, we quantitated expression of 800 human miRNAs in formalin-fixed paraffin-embedded tissue RNA using NanoString miRNA v2. We tested differences in detection by case group using the χ(2) test and differences in expression using the Wilcoxon rank-sum test. Bonferroni-corrected statistical significance threshold was set at P < 6.25E-05. Sensitivity and specificity were assessed for the most significant miRNAs using 5-fold cross-validation.
  
  
  RESULTS
  We observed 46 distinct miRNAs significantly increased in esophageal adenocarcinoma compared with Barrett's esophagus, 35 of which remained when restricted to T1b and T2 malignancies. Three miRNAs (miR-663b, miR-421, and miR-502-5p) were detected in >80% esophageal adenocarcinoma, but <20% of Barrett's esophagus. Seven miRNAs (miR-4286, miR-630, miR-575, miR-494, miR-320e, miR-4488, and miR-4508) exhibited the most extreme differences in expression with >5-fold increases. Using 5-fold cross-validation, we repeated feature (miR) selection and case-control prediction and computed performance criteria. Each of the five folds selected the same top 10 miRNAs, which, together, provided 98% sensitivity and 95% specificity.
  
  
  CONCLUSIONS
  This study provides evidence that tissue miRNA profiles can discriminate esophageal adenocarcinoma from Barrett's esophagus. This large analysis has identified miRNAs that merit further investigation in relation to pathogenesis and diagnosis of esophageal adenocarcinoma.
  
  
  CONCLUSIONS
  These candidate miRNAs may provide a means for improved risk stratification and more cost-effective surveillance.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DDHS, Bethesda, Maryland. jennifer.drahos@nih.gov.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Drahos
authors.affiliation: Department of Surgery, Upper-GI-Service, CCC-GET Unit, Medical University of Vienna, Vienna, Austria.
authors.forename: Katrin
authors.initials: K
authors.lastname: Schwameis
authors.affiliation: Johns Hopkins Medical Institutions Deep Sequencing and Microarray Core, Baltimore, Maryland.
authors.forename: Linda D
authors.initials: LD
authors.lastname: Orzolek
authors.affiliation: Johns Hopkins Medical Institutions Deep Sequencing and Microarray Core, Baltimore, Maryland.
authors.forename: Haiping
authors.initials: H
authors.lastname: Hao
authors.affiliation: Department of Surgery, Upper-GI-Service, CCC-GET Unit, Medical University of Vienna, Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Birner
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DDHS, Bethesda, Maryland.
authors.forename: Phillip R
authors.initials: PR
authors.lastname: Taylor
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DDHS, Bethesda, Maryland.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Pfeiffer
authors.affiliation: Department of Surgery, Upper-GI-Service, CCC-GET Unit, Medical University of Vienna, Vienna, Austria.
authors.forename: Sebastian F
authors.initials: SF
authors.lastname: Schoppmann
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DDHS, Bethesda, Maryland.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Cook
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D001471:Barrett Esophagus / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*
chemical_list: D035683:MicroRNAs