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

Diane Mege (1, 2) , Lydie Crescence (1, 2) , Mehdi Ouaissi (3) , Igor Sielezneff (1, 2) , Régis Guieu (4) , Francoise Dignat-George (1, 2) , Christophe Dubois (1, 2) , Laurence Panicot-Dubois (1, 2)

1 VRCM - Vascular research center of Marseille
2 Physiopathologie de l'Endothelium
3 TIMONE - Hôpital de la Timone [CHU - APHM]
4 DS-ACI / UMR MD2 - Dysoxie, suractivité : aspects cellulaires et intégratifs thérapeutiques

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.

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

Domaines: Sciences du Vivant [q-bio]; Cancer; Hépatologie et Gastroentérologie

Diane Mege, Lydie Crescence, Mehdi Ouaissi, Igor Sielezneff, Régis Guieu, et al.. Fibrin-bearing microparticles: marker of thrombo-embolic events in pancreatic and colorectal cancers. Oncotarget, 2017, 8 (57), pp.97394-97406. ⟨10.18632/oncotarget.22128⟩. ⟨hal-01770080⟩