Oncotarget

Research Papers:

Fibrin-bearing microparticles: marker of thrombo-embolic events in pancreatic and colorectal cancers

Diane Mege, Lydie Crescence, Mehdi Ouaissi, Igor Sielezneff, Regis Guieu, Françoise Dignat-George, Christophe Dubois _ and Laurence Panicot-Dubois

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Oncotarget. 2017; 8:97394-97406. https://doi.org/10.18632/oncotarget.22128

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Abstract

Diane Mege1,2, Lydie Crescence1, Mehdi Ouaissi2, Igor Sielezneff1,2, Regis Guieu3, Françoise Dignat-George1,4, Christophe Dubois1 and Laurence Panicot-Dubois1

1Aix Marseille Univ, INSERM UMR-S1076, VRCM, Marseille, France

2Department of digestive surgery, Timone University Hospital, Marseille, France

3Aix Marseille Univ, UMR MD2, Laboratory of Biochemistry, Timone University Hospital, Marseille, France

4Laboratory of Hematology, Conception University Hospital, Marseille, France

Correspondence to:

Christophe Dubois, email: christophe.dubois@univ-amu.fr

Keywords: microparticle; pancreatic cancer; colorectal cancer; thrombo-embolic events; D-dimers

Received: February 08, 2017    Accepted: August 04, 2017    Published: October 26, 2017

ABSTRACT

Background: Microparticles (MPs) are plasma membrane-derived extracellular vesicles present in the bloodstream. We have described a specific signature of MPs, called microparticulosome, in colorectal (CRC) and pancreatic (PC) cancers. We observed that levels of fibrin-bearing MPs were significantly increased in patients suffering from PC and CRC in comparison with control groups. Here, we hypothesised that fibrin-MPs may constitute a relevant biomarker of thrombosis associated with cancer. The objective was to compare the microparticulosome signature between patients presenting with thrombo-embolic event and those without.

Methods: Patients with CRC and PC were prospectively included and divided in those with thrombo-embolic events (Group A) and those without (Group B).

MPs were analyzed by flow cytometer, combining the analysis of Annexin V-positive with characterization of their origin and determination of their procoagulant activities. D-dimer levels were measured in the same samples.

Results: We included 118 patients, divided in 19 patients with thrombo embolic event and 99 patients without. Fibrin-bearing MPs levels were significantly higher in presence of thrombo-embolic events, contrary to D-dimers levels. Fibrin-bearing MPs were more frequently produced by erythrocytes, endothelial cells or Ep-CAM+cells than platelets or leukocytes. Overall survival was shorter in case of thrombo-embolic events than without. The most frequent genes expressed by MPs derived from PC or CRC were implicated in metastatic diffusion of tumor cells, drug resistance, coagulation and inflammation.

Conclusion: Circulating MPs, particularly fibrin-bearing MPs, could be used as a new biomarker to predict cancer-associated thrombo-embolic events and poor survival.


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