title: Circulating Serum Exosomal miRNAs As Potential Biomarkers for Esophageal Adenocarcinoma.
abstract: BACKGROUND
  The poor prognosis and rising incidence of esophageal adenocarcinoma highlight the need for improved detection methods. The potential for circulating microRNAs (miRNAs) as biomarkers in other cancers has been shown, but circulating miRNAs have not been well characterized in esophageal adenocarcinoma. We investigated whether circulating exosomal miRNAs have potential to discriminate individuals with esophageal adenocarcinoma from healthy controls and non-dysplastic Barrett's esophagus.
  
  
  METHODS
  Seven hundred fifty-eight miRNAs were profiled in serum circulating exosomes from a cohort of 19 healthy controls, 10 individuals with Barrett's esophagus, and 18 individuals with locally advanced esophageal adenocarcinoma. MiRNA expression was assessed using all possible permutations of miRNA ratios per individual. Four hundred eight miRNA ratios were differentially expressed in individuals with cancer compared to controls and Barrett's esophagus (Mann-Whitney U test, P < 0.05). The 179/408 ratios discriminated esophageal adenocarcinoma from healthy controls and Barrett's esophagus (linear regression, P < 0.05; area under receiver operating characteristic (ROC) > 0.7, P < 0.05). A multi-biomarker panel (RNU6-1/miR-16-5p, miR-25-3p/miR-320a, let-7e-5p/miR-15b-5p, miR-30a-5p/miR-324-5p, miR-17-5p/miR-194-5p) demonstrated enhanced specificity and sensitivity (area under ROC = 0.99, 95% CI 0.96-1.0) over single miRNA ratios to distinguish esophageal adenocarcinoma from controls and Barrett's esophagus.
  
  
  CONCLUSIONS
  This study highlights the potential for serum exosomal miRNAs as biomarkers for the detection of esophageal adenocarcinoma.
authors.affiliation: Department of Surgery, Flinders University, Room 3D211, Flinders Medical Centre, Bedford Park, Adelaide, South Australia, 5042, Australia.
authors.forename: Karen
authors.initials: K
authors.lastname: Chiam
authors.forename: Tingting
authors.initials: T
authors.lastname: Wang
authors.forename: David I
authors.initials: DI
authors.lastname: Watson
authors.forename: George C
authors.initials: GC
authors.lastname: Mayne
authors.forename: Tanya S
authors.initials: TS
authors.lastname: Irvine
authors.forename: Tim
authors.initials: T
authors.lastname: Bright
authors.forename: Lorelle
authors.initials: L
authors.lastname: Smith
authors.forename: Imogen A
authors.initials: IA
authors.lastname: White
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Bowen
authors.forename: Dorothy
authors.initials: D
authors.lastname: Keefe
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Thompson
authors.forename: Michael E
authors.initials: ME
authors.lastname: Jones
authors.forename: Damian J
authors.initials: DJ
authors.lastname: Hussey
mesh_terms: D000230:Adenocarcinoma / Q000097:blood* / Q000175:diagnosis; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D001471:Barrett Esophagus / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000097:blood* / Q000175:diagnosis; D055354:Exosomes; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D012372:ROC Curve
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs