Circulating Endothelial Cells and Procoagulant Microparticles in Patients with Glioblastoma: Prognostic Value

Abstract

AimCirculating 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.MethodsPeripheral 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.ResultsPretreatment 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 99th 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).ConclusionLevels of circulating endothelial cells may have prognostic value in patients with glioblastoma.

Small But Mighty: Microparticles as Mediators of Tumor Progression

“…In a recent study by Reynés et al peripheral blood MP levels were shown to be significantly higher in patients with glioblastoma. Following treatment, MP levels were shown to decrease, however, no data was reported with respect to the correlation with overall survival, probably due to the aggressive phenotype of such tumors [102]. Similar results were also reported by Shao et al who described that exosomes and MPs from tumor origin were elevated in glioblastoma patients, but their levels markedly decreased upon treatment.…”

Microparticles in cancer: A review of recent developments and the potential for clinical application

“…Circulating MPs have been detected in the blood, urine and ascites of cancer patients [26,[59][60][61][62]. Furthermore, elevated levels of circulating MPs have been detected in patients with non-small cell lung carcinoma [63] and newly diagnosed glioblastoma patients [64] compared to healthy controls. Additionally, breast cancer patients have higher levels of MPs than healthy controls or patients with benign breast tumors [65][66][67].…”

Phase II trial of irinotecan and metronomic temozolomide in patients with recurrent glioblastoma

“…MP levels and MP-related procoagulant activity were also elevated. We had previously observed increased numbers of MPs in patients with GB after surgery, before starting radiation therapy and TMZ [15]. Nevertheless, none of these markers showed associations with clinical outcome.…”

“…The MP-mediated procoagulant activity of plasma was analyzed by thrombin generation assay without added exogenous tissue factor or phospholipids (Calibrated Automated Thrombogram; Thrombinoscope BV, Paris, France), as previously described [15].…”