Tumor Biology

, Volume 36, Issue 6, pp 4643–4653 | Cite as

Exosomal onco-miRs from serum of patients with adenocarcinoma of the esophagus: comparison of miRNA profiles of exosomes and matching tumor

  • Ute Warnecke-Eberz
  • Seung-Hun Chon
  • Arnulf H. Hölscher
  • Uta Drebber
  • Elfriede Bollschweiler
Research Article


Diagnostic markers are needed for achieving a cure in esophageal cancer, detecting tumor cells earlier. Exosomes are bioactive vesicles secreted by cells into surrounding body fluids. Exosome formation, cargo content, and delivery have major impact in cancer development. This is the first isolation of exosomes from serum of patients with adenocarcinoma of the esophagus and comparison of exosomal miRNA profiles with matching primary tumor and normal tissues. RNA was extracted for miRNA profiling by real-time TaqMan miR arrays. The miR profiles of exosomal cargo, matching tumor, and normal tissue of a subgroup of adenocarcinoma patients have been compared. “Exosomal onco-miRs” such as miR-223-5p, miR-223-3p, miR-483-5p, miR-409-3p, miR-196b-5p, miR-192-5p, miR-146a-5p, and miR-126-5p have been identified as part of exosomal cargo being overexpressed in corresponding tumor compared to normal. Upregulation of miR-223-5p and miR-483-5p in adenocarcinoma (p = 0.034, p = 0.017) has been verified by an independent cohort of 43 patients with T2-3 adeno- and squamous cell carcinoma. In contrast, miR-224-5p, miR-452-5p, miR-23b-5p, miR-203-5p, miR-1201-5p, miR-149-5p, miR-671-3p, miR-944-5p, miR-27b-3p, and miR-22-3p have been identified to be significantly downregulated in adenocarcinoma versus normal and merely or not detectable in exosomes. “Exosomal onco-miRs” are a novel, stable, and noninvasive source for diagnosis and therapy monitoring of esophageal cancer. Oncogenic shuttle miRNAs present in exosomes may contribute to understanding how tumor cells spread their oncogenic potential to the environment. The “exosomal onco-miRs” identified seem to play a major role and may be applied for noninvasive diagnosis and therapy monitoring of adenocarcinoma of the esophagus.


Esophageal cancer Diagnostic marker Oncosomes miRNA profiling 


CD9, 63, 81

Cluster of differentiation 9, 63, 81


Cycle threshold


Computer tomography


Esophageal adenocarcinoma


Transcription factor


Enzyme-linked immunosorbent assay


Esophageal squamous cell carcinoma


F-box and WD repeat domain-containing 7


Formalin-fixed paraffin-embedded




Metalloproteinase 9


Nanoparticle tracking analysis


Tyrosine-protein phosphatase non-receptor type 1


Reverse transcription


Real-time polymerase chain reaction


Squamous cell lung carcinoma


Tumor susceptibility gene 101


Tumor stage


Upstream stimulatory factor 2


3′ untranslated region


Vascular endothelial growth factor C



We acknowledge Dr. Thomas Benen, Malven Instruments, Herrenberg, for the skillful introduction of NSA instrument for visualization and specification of size and concentration of the exosome samples. We are thankful for excellent technical assistance of Michaela Heitmann, Susanne Neiß, and Anke Wienand-Dorweiler.

Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Ute Warnecke-Eberz
    • 1
    • 3
  • Seung-Hun Chon
    • 1
  • Arnulf H. Hölscher
    • 1
  • Uta Drebber
    • 2
  • Elfriede Bollschweiler
    • 1
  1. 1.General, Visceral and Cancer SurgeryUniversity Hospital of CologneCologneGermany
  2. 2.Institute for Pathology, Center for Integrated Oncology (CIO)University Hospital of CologneCologneGermany
  3. 3.Laboratory for Molecular Oncology, General, Visceral and Cancer SurgeryUniversity Hospital of Cologne (CIO)CologneGermany

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