Z Gastroenterol 2017; 55(08): e57-e299
DOI: 10.1055/s-0037-1604757
Kurzvorträge
Ösophagus und Magen
Biomarker für Krankheitsrisiko und Prognose bei Ösophagus- und Magenkarzinom: Freitag, 15 September 2017, 10:10 – 11:30, Florenz/Forschungsforum 3
Georg Thieme Verlag KG Stuttgart · New York

Exosomal Glypican-3 is a diagnostic and prognostic biomarker in gastric cancer

M Rahbari
1   Universitätsklinikum Carl Gustav Carus, TU Dresden, Klinik u. Poliklinik für Viszeral-, Thorax- und Gefäßchirurgie, Dresden, Deutschland
,
M Pecqueux
1   Universitätsklinikum Carl Gustav Carus, TU Dresden, Klinik u. Poliklinik für Viszeral-, Thorax- und Gefäßchirurgie, Dresden, Deutschland
,
C Reissfelder
1   Universitätsklinikum Carl Gustav Carus, TU Dresden, Klinik u. Poliklinik für Viszeral-, Thorax- und Gefäßchirurgie, Dresden, Deutschland
,
T Welsch
1   Universitätsklinikum Carl Gustav Carus, TU Dresden, Klinik u. Poliklinik für Viszeral-, Thorax- und Gefäßchirurgie, Dresden, Deutschland
,
J Weitz
1   Universitätsklinikum Carl Gustav Carus, TU Dresden, Klinik u. Poliklinik für Viszeral-, Thorax- und Gefäßchirurgie, Dresden, Deutschland
,
NN Rahbari
1   Universitätsklinikum Carl Gustav Carus, TU Dresden, Klinik u. Poliklinik für Viszeral-, Thorax- und Gefäßchirurgie, Dresden, Deutschland
,
C Kahlert
1   Universitätsklinikum Carl Gustav Carus, TU Dresden, Klinik u. Poliklinik für Viszeral-, Thorax- und Gefäßchirurgie, Dresden, Deutschland
› Author Affiliations
Further Information

Publication History

Publication Date:
02 August 2017 (online)

 

Background:

Exosomes are nanosized membranous vesicles of endosomal origin. They are released by cancer cells and transport RNA, DNA and proteins of their cellular origin. Exosomes have therefore gained increasing attention as non-invasive biomarkers in cancer. Glypcian-3 is a proteoglycan, which has been described as a tumor suppressor gene in gastric cancer. Moreover, Glypican-3 shows a decreased expression in gastric cancer. The value of exosomal Glypican-3 (eGCP-3) as diagnostic and prognostic biomarker in patients with gastric cancer has not been investigated yet.

Methods:

Exosomes were isolated from serum samples of patients with gastric cancer (n = 49) who underwent surgical resection and from healthy donors (n = 56) with no evidence of neoplastic disease. The detection of exosomes was confirmed by nanoparticle-tracking analysis, western blotting (CD9, CD63, CD81 and TSG101) and FACS analysis (CD9, CD63, CD81 TSG101) in selected samples (n = 15). Subsequently, the expression of eGCP-3 was assessed by FACS in the entire cohort. Furthermore, expression of eGCP-3 was evaluated and correlated to clinicopathologic parameters.

Results:

The detection of serum exosomes was confirmed by nanoparticle-tracking analysis, western blotting and FACS. We show that Glypican-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 eGCP-3 of gastric cancer patients with healthy donors, outperforming current standard biomarkers (CEA, CA 19 – 9 and CA 72 – 4). Additionally, analyses of clinicopathologic parameters revealed expression of eGCP-3 of being associated with advanced UICC tumor stage (p = 0.012).

On univariate analysis, low eGCP-3 expression was associated significantly with poor overall survival (p = 0.041). Cox regression analysis significantly confirmed eGCP-3 as an independent prognostic marker.

Conclusion:

Our study for the first time suggests eGCP-3 as a potential diagnostic and prognostic biomarker in gastric cancer. For the clinical integration of the given findings, further validation studies are mandatory.