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

Abstract

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.

Keywords

Esophageal cancer Diagnostic marker Oncosomes miRNA profiling 

Abbreviations

CD9, 63, 81

Cluster of differentiation 9, 63, 81

Ct

Cycle threshold

CT

Computer tomography

EAC

Esophageal adenocarcinoma

E2F1

Transcription factor

ELISA

Enzyme-linked immunosorbent assay

ESCC

Esophageal squamous cell carcinoma

FBXW7

F-box and WD repeat domain-containing 7

FFPE

Formalin-fixed paraffin-embedded

MIR

MicroRNA

MMP-9

Metalloproteinase 9

NTA

Nanoparticle tracking analysis

PTPN1

Tyrosine-protein phosphatase non-receptor type 1

RT

Reverse transcription

RT-PCR

Real-time polymerase chain reaction

SCLC

Squamous cell lung carcinoma

TSG101

Tumor susceptibility gene 101

T

Tumor stage

USF2

Upstream stimulatory factor 2

3′UTR

3′ untranslated region

VEGFC

Vascular endothelial growth factor C

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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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