Journal of Gastrointestinal Surgery

, Volume 19, Issue 7, pp 1208–1215 | Cite as

Circulating Serum Exosomal miRNAs As Potential Biomarkers for Esophageal Adenocarcinoma

  • Karen Chiam
  • Tingting Wang
  • David I. Watson
  • George C. Mayne
  • Tanya S. Irvine
  • Tim Bright
  • Lorelle Smith
  • Imogen A. White
  • Joanne M. Bowen
  • Dorothy Keefe
  • Sarah K. Thompson
  • Michael E. Jones
  • Damian J. Hussey
Original Article



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.


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.


This study highlights the potential for serum exosomal miRNAs as biomarkers for the detection of esophageal adenocarcinoma.


Esophageal cancer Barrett’s esophagus Biomarkers microRNAs Exosomes Serum 


Author Contributions

All authors participated in aspects of study design, data acquisition and analysis, and preparation of the manuscript.


This work was supported by a Project grant (APP1022720) and a Centres of Research Excellence grant (APP1040947), both awarded by the National Health and Medical Research Council of Australia, and a Strategic Research Partnership Grant awarded by the Cancer Council of New South Wales.

Supplementary material

11605_2015_2829_MOESM1_ESM.doc (69 kb)
Supplementary Table 1 Predicted probability that each left-out patient in the leave-one-out cross validation has cancer. Each probability was determined using a regression model of a five miRNA ratio panel derived with the sequential testing method utilized in this study. Out of the 18 actual cancer patients in the cohort, the leave-one-out cross validation correctly identified 13 cancer patients from the 18 individuals (highlighted in gray) with the highest predicted probabilities of being a cancer based on the regression model. (DOC 69 kb)
11605_2015_2829_MOESM2_ESM.doc (89 kb)
Supplementary Figure 1 Distribution (a) and normality plots (b) of the standardized residuals of the combined five miRNA ratios biomarker panel. (DOC 89 kb)
11605_2015_2829_MOESM3_ESM.doc (395 kb)
Supplementary Figure 2 Distribution of the five miRNA ratios in healthy controls, Barrett’s esophagus and esophageal adenocarcinoma. (DOC 395 kb)
11605_2015_2829_MOESM4_ESM.doc (60 kb)
Supplementary Figure 3 LOOCV prediction errors for increasing numbers of ratios in the final regression model. Error rate is the number of cancers that were misclassified, as a percentage. (DOC 59 kb)


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Copyright information

© The Society for Surgery of the Alimentary Tract 2015

Authors and Affiliations

  • Karen Chiam
    • 1
  • Tingting Wang
    • 1
  • David I. Watson
    • 1
  • George C. Mayne
    • 1
  • Tanya S. Irvine
    • 1
  • Tim Bright
    • 1
  • Lorelle Smith
    • 1
    • 5
  • Imogen A. White
    • 2
  • Joanne M. Bowen
    • 3
  • Dorothy Keefe
    • 4
  • Sarah K. Thompson
    • 5
  • Michael E. Jones
    • 6
    • 7
  • Damian J. Hussey
    • 1
  1. 1.Department of SurgeryFlinders UniversityAdelaideAustralia
  2. 2.School of MedicineUniversity of AdelaideAdelaideAustralia
  3. 3.University of Adelaide School of Medical SciencesAdelaideAustralia
  4. 4.Royal Adelaide Hospital Cancer CentreAdelaideAustralia
  5. 5.Discipline of SurgeryUniversity of AdelaideAdelaideAustralia
  6. 6.Department of Anaesthesia and Pain MedicineFlinders UniversityAdelaideAustralia
  7. 7.Department of Anatomy and HistologyFlinders UniversityAdelaideAustralia

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