Circulating endothelial cells and procoagulant microparticles in patients with glioblastoma: prognostic value

• Published in: PloS one Vol. 8; no. 7; p. e69034
• Main Authors: Reynés, Gaspar, Vila, Virtudes, Fleitas, Tania, Reganon, Edelmiro, Font de Mora, Jaime, Jordá, María, Martínez-Sales, Vicenta
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 29.07.2013; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Aged, 80 and over; Angiogenesis; Biomarkers; Biomarkers, Tumor - blood; Blood; Blood Coagulation; Blood platelets; Brain cancer; Brain Neoplasms - blood; Brain Neoplasms - pathology; Cancer; Cancer therapies; Case-Control Studies; Cell-Derived Microparticles - metabolism; Chemotherapy; Clotting; Colorectal cancer; Cytometry; DNA methylation; DNA Modification Methylases - genetics; DNA Repair Enzymes - genetics; Drug dosages; Endothelial cells; Endothelial Cells - pathology; Female; Flow cytometry; Glioblastoma; Glioblastoma - blood; Glioblastoma - pathology; Humans; Immunofluorescence; Kaplan-Meier Estimate; Male; Medical prognosis; Medicine; Microparticles; Microscopy; Middle Aged; Multiplexing; NMR; Nuclear magnetic resonance; Patients; Peripheral blood; Phospholipids; Prognosis; Prostate cancer; Radiation therapy; Surgery; Survival; Temozolomide; Thrombin; Thrombosis; Treatment Outcome; Tumor Suppressor Proteins - genetics
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0069034

Circulating endothelial cells and microparticles are prognostic factors in cancer. However, their prognostic and predictive value in patients with glioblastoma is unclear. The objective of this study was to investigate the potential prognostic value of circulating endothelial cells and microparticles in patients with newly diagnosed glioblastoma treated with standard radiotherapy and concomitant temozolomide. In addition, we have analyzed the methylation status of the MGMT promoter. Peripheral blood samples were obtained before and at the end of the concomitant treatment. Blood samples from healthy volunteers were also obtained as controls. Endothelial cells were measured by an immunomagnetic technique and immunofluorescence microscopy. Microparticles were quantified by flow cytometry. Microparticle-mediated procoagulant activity was measured by endogen thrombin generation and by phospholipid-dependent clotting time. Methylation status of MGMT promoter was determined by multiplex ligation-dependent probe amplification. Pretreatment levels of circulating endothelial cells and microparticles were higher in patients than in controls (p<0.001). After treatment, levels of microparticles and thrombin generation decreased, and phospholipid-dependent clotting time increased significantly. A high pretreatment endothelial cell count, corresponding to the 99(th) percentile in controls, was associated with poor overall survival. MGMT promoter methylation was present in 27% of tumor samples and was associated to a higher overall survival (66 weeks vs 30 weeks, p<0.004). Levels of circulating endothelial cells may have prognostic value in patients with glioblastoma.