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

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.

Keywords

Esophageal cancer Barrett’s esophagus Biomarkers microRNAs Exosomes Serum 

Supplementary material

11605_2015_2829_MOESM1_ESM.doc (69 kb)
Supplementary Table 1Predicted 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 1Distribution (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 2Distribution 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 3LOOCV 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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