Z Gastroenterol 2018; 56(08): e301-e302
DOI: 10.1055/s-0038-1668920
Kurzvorträge
Gastroenterologische Onkologie
Ösophagus- und Magenkarzinom: Therapierelevante Grundlagenforschung – Freitag, 14. September 2018, 12:40 – 13:52, 22b
Georg Thieme Verlag KG Stuttgart · New York

Expression of Glypican-3 is an independent prognostic biomarker in primary gastric cancer and corresponding serum exosomes

M Rahbari
1   Universitätsklinikum Carl Gustav Carus, Medizinische Fakultät, Technische Universität Dresden, Klinik u. Poliklinik für Viszeral-, Thorax- und Gefäßchirurgie, Dresden, Deutschland
,
D Aust
2   Universitätsklinikum Carl Gustav Carus, Medizinische Fakultät, Technische Universität Dresden, Institut für Pathologie, Dresden, Deutschland
,
NN Rahbari
3   Universitätsmedizin Mannheim, Chirurgische Klinik, Mannheim, Deutschland
,
J Weitz
1   Universitätsklinikum Carl Gustav Carus, Medizinische Fakultät, Technische Universität Dresden, Klinik u. Poliklinik für Viszeral-, Thorax- und Gefäßchirurgie, Dresden, Deutschland
,
C Kahlert
1   Universitätsklinikum Carl Gustav Carus, Medizinische Fakultät, Technische Universität Dresden, Klinik u. Poliklinik für Viszeral-, Thorax- und Gefäßchirurgie, Dresden, Deutschland
› Author Affiliations
Further Information

Publication History

Publication Date:
13 August 2018 (online)

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    Background:

    Exosomes are nano-sized membranous vesicles of endosomal origin and released by cancer cells for the transfer RNA, DNA and proteins of their cellular origin. Exosomes have therefore gained increasing attention as non-invasive biomarkers in cancer. The expression of Glypcian-3 (GPC-3), a Heparane-Sulfate-Proteoglycan (HSPG), has been associated with varying survival outcomes in gastric cancer (GC). The value of exosomal Glypican-3 (eGPC-3) and tissue based Glypican-3 (tGPC-3) as diagnostic and prognostic biomarkers in patients with GC has not been investigated yet.

    Methods:

    Exosomes were isolated from serum samples of patients with GC or adenocarcinoma of the esophagogastric junction (AEG) (n = 49) who underwent surgical resection and from control subjects (n = 56) with no evidence of neoplastic disease. The detection of exosomes was confirmed by nanoparticle-tracking analysis (NTA), transmission electron microscope (TEM), western blotting (CD9, CD63 and TSG101) and fluorescent nanoparticle-tracking analysis (fNTA) (CD9, CD63 and TSG101) in representative samples. Subsequently, the expression of eGPC-3 was assessed by flow cytometry as well as the expression of GPC-3 on gastric cancer tissue specimens by immunohistochemistry (IHC). Furthermore, expression of tGPC-3 has been correlated to clinicopathologic parameters and validated in two independent external control populations.

    Results:

    The presence of exosomes could be confirmed by NTA, TEM, western blotting and fNTA. We show that GPC-3 is significantly decreased on serum exosomes from gastric cancer patients compared to healthy donors (p < 0.0001). ROC curve analysis resulted in an AUC of 0.85 when comparing eGPC-3 of gastric cancer patients with healthy donors, outperforming current standard biomarkers (CEA, CA 19 – 9 and CA 72 – 4).

    On univariate analysis, low eGPC-3 and high tGPC-3 expression was associated significantly with poor overall survival (p = 0.041). High expression of tGPC-3 was validated as strong prognostic factor in two independent cohorts. Cox regressional analysis significantly confirmed tGPC-3 as an independent prognostic marker (p = 0.02).

    Conclusion:

    Our study for the first time suggests eGPC-3 and tGPC-3 as potential diagnostic and prognostic biomarkers for GC and AEG.


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