INSERM, UMRS 872, CRC, Université Pierre et Marie Curie-Paris 6, Université Paris Descartes, Paris, France.
Cancer Med. 2012 Oct;1(2):261-7. doi: 10.1002/cam4.11. Epub 2012 Jul 23.
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.
血浆可溶性内皮蛋白 C 受体（sEPCR）水平升高可能是血栓形成风险的一个指标。本研究旨在将白血病相关高凝状态与高水平血浆 sEPCR 相关联，并提出在常规临床实践中测量其的方法。通过流式细胞术、免疫细胞化学和逆转录聚合酶链反应（RT-PCR）来确定白血病细胞系中的 EPCR 表达。还确定了候选细胞系 HL-60 的 EPCR 基因序列。通过酶联免疫吸附试验（ELISA）对 148 例血液系统恶性肿瘤患者和 101 例健康志愿者的 76 份血浆样本和 72 份骨髓抽吸物进行了 sEPCR 和 D-二聚体的回顾性分析。所有白血病细胞系均表达 EPCR。此外，HL-60 EPCR 基因序列与内皮参考基因有广泛的相似性。在启动子和内含子区域发现了所有最初描述的单核苷酸多态性（SNP）和一些新的 SNP。在这些患者中，67%的患者血浆 sEPCR 水平高于对照组（100±28ng/mL），其中 16.3%的患者曾发生过血栓事件。这些患者被分为三组：组 1（n=45），血浆 sEPCR 量低于 100ng/mL；组 2（n=45），sEPCR 浓度在 100-200ng/mL 之间；组 3（n=20），浓度大于 200ng/mL。每组记录的血栓发生率分别为 4、6 和 8 例。这些结果表明，EPCR 不仅表达于广泛的人类恶性血液细胞中，而且检测血浆 sEPCR 水平还可深入了解癌症患者的血栓形成风险，尤其是当 sEPCR 水平超过 200ng/mL 时。
