Soluble endothelial protein C receptor (sEPCR) is likely a biomarker of cancer‐associated hypercoagulability in human hematologic malignancies

Abstract

Elevated plasma level of soluble endothelial protein C receptor (sEPCR) may be an indicator of thrombotic risk. The present study aims to correlate leukemia-associated hypercoagulability to high level plasma sEPCR and proposes its measurement in routine clinical practice. EPCR expressions in leukemic cell lines were determined by flow cytometry, immunocytochemistry, and reverse transcription polymerase chain reaction (RT-PCR). EPCR gene sequence of a candidate cell line HL-60 was also determined. Plasma samples (n = 76) and bone marrow aspirates (n = 72) from 148 patients with hematologic malignancies and 101 healthy volunteers were analyzed by enzyme-linked immunosorbent assay (ELISA) via a retrospective study for sEPCR and D-dimer. All leukemic cell lines were found to express EPCR. Also, HL-60 EPCR gene sequence showed extensive similarities with the endothelial reference gene. All single nucleotide polymorphisms (SNPs) originally described and some new SNPs were revealed in the promoter and intronic regions. Among these patients 67% had plasma sEPCR level higher than the controls (100 ± 28 ng/mL), wherein 16.3% patients had experienced a previous thrombotic event. These patients were divided into: group-1 (n = 45) with amount of plasmatic sEPCR below 100 ng/mL, group-2 (n = 45) where the concentration of sEPCR was between 100 and 200, and group-3 (n = 20) higher than 200 ng/mL. The numbers of thrombotic incidence recorded in each group were four, six, and eight, respectively. These results reveal that EPCR is expressed not only by a wide range of human malignant hematological cells but also the detection of plasma sEPCR levels provides a powerful insight into thrombotic risk assessment in cancer patients, especially when it surpasses 200 ng/mL.

Endothelial protein C receptor gene 6936A/G single-nucleotide polymorphism as a possible biomarker of thrombotic risk in acute myeloid leukemia

“…In a previous study, we reported that malignant cells express and secrete EPCR and that sEPCR is associated with hypercoagulability in human hematological malignancies (10,11). We also reported that the EPCR gene sequence of HL-60 myeloblastic leukemia cells is quite identical to that of endothelial cells, in that it harbors the different SNPs (11) as previously reported for the endothelial cell gene (12).…”

“…We previously reported that EPCR is expressed in human malignant blood cells, often resulting in higher plasma sEPCR levels (11). Using a retrospective clinical study (n=110), we observed that, when the plasma sEPCR level rises above the 200 ng/ml threshold, the risk of thrombosis also rises considerably (40%) in hematological pathologies (11).…”

Ankaferd Blood Stopper induces apoptosis and regulates PAR1 and EPCR expression in human leukemia cells

“…There have been few studies investigating EPCR expression in hematological malignancies [36][37][38]. In these studies they detected EPCR expression in a wide range of malignant hematological cells.…”

Assessment of Soluble Endothelial Protein C Receptor and Thrombomodulin Levels in Newly Diagnosed Myeloproliferative Neoplasms

“…As a substantial proportion of these patients (67%) had plasma sEPCR levels higher than controls, authors claimed that plasma sEPCR level may be a feasible marker which provides an illuminant insight into thrombotic risk assessment in patients wih hematological malignan cies. 5 Some reports have emphasized a reasonable relationship between sEPCR and TM levels and thrombotic complications. A total of 56 patients with central retinal vein occlusion (CRVO), 26 patients with branch RVO and 78 healthy subjects were enrolled in a study by Gumus et al Elevated levels of sEPCR were considered to be a risk factor for CRVO in this study.…”

“…3,[5][6][7] Although thrombohemorrhagic complications are considered as the most common causes of morbidity and mortality in MPNs, the etiology and pathogenesis of the clotting abnormalities still remain unclear. 3,[5][6][7] Clinical factors including age, previous history of thrombosis, obesity, hypertension and hyperlipidemia as well as elevated blood cell counts (leukocytosis, erythrocytosis and thrombocytoAssessment of Soluble Endothelial Protein C Receptor and Thrombomodulin Levels in Newly Diagnosed Myeloproliferative Neoplasms A AB BS S T TR RA AC CT T O Ob bj je ec ct ti iv ve e: : Thrombotic complications are considered as significant causes of morbidity and mortality in patients with myeloproliferative neoplasms (MPN). The protein C (PC) pathway plays a pivotal role in the regulation of the coagulation cascade through inactivation of factor Va and factor VIIIa, which is mediated by an intereaction between activated PC (APC) and endothelial PC receptor (EPCR).…”