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J Clin Med. 2019 May 16;8(5). pii: E696. doi: 10.3390/jcm8050696.

Expression of Glypican 3 is an Independent Prognostic Biomarker in Primary Gastro-Esophageal Adenocarcinoma and Corresponding Serum Exosomes.

Author information

1
Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technical University Dresden, D-01307 Dresden, Germany. Mohammad.Rahbari@uniklinikum-dresden.de.
2
Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technical University Dresden, D-01307 Dresden, Germany. Mathieu.Pecqueux@uniklinikum-dresden.de.
3
Institute for Pathology, University Hospital Carl Gustav Carus, Technical University Dresden, D-01307 Dresden, Germany. Daniela.Aust@uniklinikum-dresden.de.
4
Tumor and Normal Tissue Bank of the University Cancer Center, Technical University Dresden, D-01307 Dresden, Germany. Daniela.Aust@uniklinikum-dresden.de.
5
Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Bautzner Landstrasse 400, D-01328 Dresden, Germany. h.stephan@hzdr.de.
6
Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Technical University Dresden, D-01307 Dresden, Germany. oliver.tiebel@uniklinikum-dresden.de.
7
Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, Technical University Dresden, D-01307 Dresden, Germany. antonios.chatzigeorgiou@uniklinikum-dresden.de.
8
Institute for Transfusion Medicine, German Red Cross Blood Donation Service North-East, D-01307 Dresden, Germany. t.tonn@blutspende.de.
9
Medical Faculty, University Hospital Carl Gustav Carus, Technical University Dresden, D-01307 Dresden, Germany. t.tonn@blutspende.de.
10
Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technical University Dresden, D-01307 Dresden, Germany. Franziska.Baenke@uniklinikum-dresden.de.
11
German Cancer Consortium (DKTK) German Cancer Research Centre (DKFZ), D-69120 Heidelberg, Germany. Franziska.Baenke@uniklinikum-dresden.de.
12
Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technical University Dresden, D-01307 Dresden, Germany. Rao.Venkatesh@uniklinikum-dresden.de.
13
Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technical University Dresden, D-01307 Dresden, Germany. Nicole.Ziegler@uniklinikum-dresden.de.
14
German Cancer Consortium (DKTK) German Cancer Research Centre (DKFZ), D-69120 Heidelberg, Germany. Nicole.Ziegler@uniklinikum-dresden.de.
15
Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technical University Dresden, D-01307 Dresden, Germany. Helena.Greif@uniklinikum-dresden.de.
16
Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technical University Dresden, D-01307 Dresden, Germany. Kuailu.Lin@uniklinikum-dresden.de.
17
Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technical University Dresden, D-01307 Dresden, Germany. Juergen.Weitz@uniklinikum-dresden.de.
18
Department of Surgery, University Medicine Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, D-68167 Mannheim, Germany. Nuh.Rahbari@umm.de.
19
Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technical University Dresden, D-01307 Dresden, Germany. Christoph.Kahlert@uniklinikum-dresden.de.
20
German Cancer Consortium (DKTK) German Cancer Research Centre (DKFZ), D-69120 Heidelberg, Germany. Christoph.Kahlert@uniklinikum-dresden.de.

Abstract

Exosomes are nano-sized membranous vesicles of endosomal origin that carry nucleic acids, lipids and proteins. The cargo of exosomes is cell origin specific and the release of these exosomes and uptake by an acceptor cell is seen as a vital element of cell-cell communication. Here, we sought to investigate the diagnostic and prognostic value of the expression of glypican 3 (GPC3) on primary gastro-esophageal adenocarcinoma (GEA) tissue (tGPC3) and corresponding serum exosomes (eGPC3). Circulating exosomes were extracted from serum samples of 49 patients with GEA and 56 controls. Extracted exosomes were subjected to flow cytometry for the expression of eGPC3 and GPC3 expression on primary GEA tissue samples was determined by immunohistochemistry and correlated to clinicopathological parameters. We found decreased eGPC3 levels in GEA patients compared to healthy controls (p < 0.0001) and high tGPC3 expression. This was significantly associated with poor overall survival (high vs. low eGPC3: 87.40 vs. 60.93 months, p = 0.041, high vs. low tGPC3: 58.03 vs. 84.70 months, p = 0.044). Cox regressional analysis confirmed tGPC3 as an independent prognostic biomarker for GEA (p = 0.02) and tGPC3 expression was validated in two independent cohorts. Our findings demonstrate that eGPC3 and tGPC3 can be used as potential diagnostic and prognostic biomarkers for GEA.

KEYWORDS:

antibody secreting cell; biomarker; breast cancer; immune profile; immunotherapy; lymph node; microarray; tumor antigen

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; the collection, analyses, or interpretation of data; the writing of the manuscript, or in the decision to publish these results.

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