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微泡相关组织因子促凝活性用于卵巢癌的术前诊断

Microvesicle-associated tissue factor procoagulant activity for the preoperative diagnosis of ovarian cancer.

作者信息

Claussen Carlota, Rausch Alma-Verena, Lezius Susanne, Amirkhosravi Ali, Davila Monica, Francis John L, Hisada Yohei M, Mackman Nigel, Bokemeyer Carsten, Schmalfeldt Barbara, Mahner Sven, Langer Florian

机构信息

II. Medizinische Klinik und Poliklinik, Onkologisches Zentrum - Universitäres Cancer Center Hamburg (UCCH), Universitätsklinikum Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany.

Klinik und Poliklinik für Gynäkologie, Zentrum für Operative Medizin, Universitätsklinikum Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany.

出版信息

Thromb Res. 2016 May;141:39-48. doi: 10.1016/j.thromres.2016.03.002. Epub 2016 Mar 2.

Abstract

BACKGROUND

Tissue factor (TF) is involved in tumor growth and metastasis and contributes to venous thromboembolism (VTE) in cancer, including gynecological malignancies. The diagnostic value of microvesicle-associated TF procoagulant activity (MV TF PCA) in women with suspected ovarian cancer, however, has not been studied.

OBJECTIVE

To evaluate MV TF PCA as a diagnostic tool in women with an ovarian mass of unknown etiology and as a predictive biomarker for perioperative VTE.

METHODS

Plasma MVs were isolated by high-speed centrifugation and analyzed for TF-specific PCA by single-stage clotting assay. In addition, plasma TF antigen and soluble P-selectin (sCD62P) were measured by ELISA.

RESULTS

D-Dimer, MV TF PCA, and sCD62P, but not the tumor marker, CA-125, significantly differentiated patients with malignant (n=40) from those with benign tumors (n=15) and healthy controls (n=34). In cancer patients, only D-Dimer and CA-125 correlated with the FIGO stage. An abnormal D-dimer had the highest sensitivity for the diagnosis of cancer, while MV TF PCA above the ROC curve-derived cut-off value of 182U/mL had the highest specificity. By multivariate logistic regression analysis, addition of MV TF PCA conferred diagnostic benefit to the single variables, CA-125 (p=0.052) and D-dimer (p=0.019). Perioperative VTE occurred in 16% of cancer patients and was associated with an advanced FIGO stage, but not MV TF PCA. There was no difference in plasma TF antigen levels between study groups.

CONCLUSIONS

MV TF PCA, but not plasma TF antigen, may provide valuable additional information for the diagnostic work-up of women with suspected ovarian cancer.

摘要

背景

组织因子(TF)参与肿瘤生长和转移,并促成癌症(包括妇科恶性肿瘤)中的静脉血栓栓塞(VTE)。然而,微泡相关TF促凝活性(MV TF PCA)在疑似卵巢癌女性中的诊断价值尚未得到研究。

目的

评估MV TF PCA作为病因不明的卵巢肿块女性的诊断工具以及围手术期VTE的预测生物标志物。

方法

通过高速离心分离血浆微泡,并通过单阶段凝血试验分析TF特异性PCA。此外,通过酶联免疫吸附测定法测量血浆TF抗原和可溶性P-选择素(sCD62P)。

结果

D-二聚体、MV TF PCA和sCD62P,而非肿瘤标志物CA-125,能显著区分恶性肿瘤患者(n = 40)与良性肿瘤患者(n = 15)及健康对照者(n = 34)。在癌症患者中,只有D-二聚体和CA-125与国际妇产科联盟(FIGO)分期相关。异常D-二聚体对癌症诊断的敏感性最高,而MV TF PCA高于曲线下面积(ROC)曲线得出的临界值182U/mL时特异性最高。通过多变量逻辑回归分析,添加MV TF PCA对单一变量CA-125(p = 0.052)和D-二聚体(p = 0.019)的诊断有帮助。16%的癌症患者发生围手术期VTE,且与FIGO晚期相关,但与MV TF PCA无关。研究组之间血浆TF抗原水平无差异。

结论

MV TF PCA而非血浆TF抗原,可能为疑似卵巢癌女性的诊断检查提供有价值的额外信息。

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