title: MicroRNA Expression can be a Promising Strategy for the Detection of Barrett's Esophagus: A Pilot Study.
abstract: OBJECTIVE
  Patient outcomes for esophageal adenocarcinoma (EAC) have not improved despite huge advances in endoscopic therapy because cancers are being diagnosed late. Barrett's esophagus (BE) is the primary precursor lesion for EAC, and thus the non-endoscopic molecular diagnosis of BE can be an important approach to improve EAC outcomes if robust biomarkers for timely diagnosis are identified. MicroRNAs (miRNAs) are tissue-specific novel biomarkers that regulate gene expression and may satisfy this requirement.
  
  
  METHODS
  Patients with gastroesophageal reflux disease (GERD) and BE were selected from an ongoing tissue and serum repository. BE was defined by the presence of intestinal metaplasia. Previously published miRNA sequencing profiles of GERD and BE patients allowed us to select three miRNAs, miR-192-5p, -215-5p, and -194-5p, for further testing in a discovery cohort and an independent validation cohort. Receiver operating curves were generated to calculate the diagnostic accuracy of these miRNAs for BE diagnosis. To test specificity, the miRNA signature was compared with those of the gastric cardia epithelium and the non-intestinal-type columnar epithelium (another definition of BE). In addition, to gain insights into BE origin (intestinal vs non-intestinal), global BE miRNA profiles were compared with the published miRNA profiles of other columnar epithelia in the gastrointestinal tract, that is, normal stomach and small and large intestine.
  
  
  RESULTS
  The discovery cohort included 67 white male patients (40 with GERD and 27 with BE). The validation cohort included 28 patients (19 with GERD and 11 with BE). In the discovery cohort, the sensitivity, specificity and area under the curve (AUC) of the three mRNAs for BE diagnosis were 92-100%, 94-95%, and 0.96-0.97, respectively. During validation, the sensitivity and specificity of miRNAs for BE diagnosis were as follows: miR-192-5p, 92% and 94%, AUC 0.94 (0.80-0.99, P=0.0004); miR-215-5p, 100% and 94%, AUC 0.98 (0.84-1, P=0.0004); and miR-194-5p, 91% and 94%, AUC 0.96 (0.80-0.99, P=0.0001), respectively. The tested miRNAs identified all BE patients in both the discovery and the validation cohorts. When compared with non intestinal-type columnar and gastric cardia epithelia, the miRNA signature was specific to the intestinal-type columnar epithelium. Comparisons of BE miRNA sequencing data to published data sets for the normal stomach, small intestine and large intestine confirmed that two of the three miRNAs (miR-215-5p and -194-5p) were specific to the intestinal-type epithelium.
  
  
  CONCLUSIONS
  MicroRNAs are highly accurate for detecting intestinal-type BE epithelia and should be tested further for the non-endoscopic molecular diagnosis of BE.
authors.affiliation: 1] Division of Gastroenterology and Hepatology, Veterans Affairs Medical Center, Kansas City, Missouri, USA [2] University of Kansas Medical Center, Kansas City, Kansas, USA [3] Kansas Cancer Institute, Kansas City, Kansas, USA.
authors.forename: Ajay
authors.initials: A
authors.lastname: Bansal
authors.affiliation: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas, USA.
authors.forename: Xiaoman
authors.initials: X
authors.lastname: Hong
authors.affiliation: Bioinformatics Core Facility, University of Kansas, Lawrence, Kansas, USA.
authors.forename: In-Hee
authors.initials: IH
authors.lastname: Lee
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Kausilia K
authors.initials: KK
authors.lastname: Krishnadath
authors.affiliation: Department of Pathology, Veterans Affairs Medical Center, Kansas City, Missouri and University of Kansas Medical Center, Kansas City, Kansas, USA.
authors.forename: Sharad C
authors.initials: SC
authors.lastname: Mathur
authors.affiliation: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas, USA.
authors.forename: Sumedha
authors.initials: S
authors.lastname: Gunewardena
authors.affiliation: 1] Division of Gastroenterology and Hepatology, Veterans Affairs Medical Center, Kansas City, Missouri, USA [2] University of Kansas Medical Center, Kansas City, Kansas, USA [3] Kansas Cancer Institute, Kansas City, Kansas, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Rastogi
authors.affiliation: 1] Division of Gastroenterology and Hepatology, Veterans Affairs Medical Center, Kansas City, Missouri, USA [2] University of Kansas Medical Center, Kansas City, Kansas, USA [3] Kansas Cancer Institute, Kansas City, Kansas, USA.
authors.forename: Prateek
authors.initials: P
authors.lastname: Sharma
authors.affiliation: 1] Kansas Cancer Institute, Kansas City, Kansas, USA [2] Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas, USA.
authors.forename: Lane K
authors.initials: LK
authors.lastname: Christenson