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

  • Research Article
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Tumor Biology

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.

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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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Acknowledgments

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.

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Authors and Affiliations

  1. General, Visceral and Cancer Surgery, University Hospital of Cologne, Kerpener Straße 62, D-50937, Cologne, Germany

    Ute Warnecke-Eberz, Seung-Hun Chon, Arnulf H. Hölscher & Elfriede Bollschweiler

  2. Institute for Pathology, Center for Integrated Oncology (CIO), University Hospital of Cologne, Kerpener Straße 62, D-50937, Cologne, Germany

    Uta Drebber

  3. Laboratory for Molecular Oncology, General, Visceral and Cancer Surgery, University Hospital of Cologne (CIO), Kerpener Strasse 62, 50937, Cologne, Germany

    Ute Warnecke-Eberz

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  1. Ute Warnecke-Eberz
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  2. Seung-Hun Chon
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  3. Arnulf H. Hölscher
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Correspondence to Ute Warnecke-Eberz.

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Warnecke-Eberz, U., Chon, SH., Hölscher, A.H. et al. Exosomal onco-miRs from serum of patients with adenocarcinoma of the esophagus: comparison of miRNA profiles of exosomes and matching tumor. Tumor Biol. 36, 4643–4653 (2015). https://doi.org/10.1007/s13277-015-3112-0

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  • DOI: https://doi.org/10.1007/s13277-015-3112-0

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