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局限性前列腺癌中的血浆组织因子抗原:分布、临床意义及与止血激活标志物的相关性

Plasma tissue factor antigen in localized prostate cancer: distribution, clinical significance and correlation with haemostatic activation markers.

作者信息

Langer Florian, Chun Felix Kyoung-Hwan, Amirkhosravi Ali, Friedrich Martin, Leuenroth Sven, Eifrig Barbara, Bokemeyer Carsten, Francis John L

机构信息

II. Medizinische Klinik und Poliklinik, Universitätsklinikum Eppendorf, Hamburg, Germany.

出版信息

Thromb Haemost. 2007 Mar;97(3):464-70.

Abstract

Tissue factor (TF) is involved in cancer growth and metastasis, and haemostatic abnormalities are found in most patients with advanced malignancies, including prostate cancer (PC). Because anti-haemostatic agents are increasingly screened for their potential to prolong survival in tumor patients, a detailed characterization of haemostatic markers in selected cancer subtypes and clinical stages is warranted. In this study, we measured preoperative plasma TF antigen in a large cohort of patients with localized PC and correlated its levels with markers of coagulation and platelet activation, prostate-specific antigen (PSA), and histopathological findings to explore its potential as a prognostic marker in this tumor entity. Out of 140 patients, 19% and 23% had plasma TF antigen levels of <40 pg/ml (low-TF) and >200 pg/ml (high-TF), respectively, which was substantially higher than in 42 healthy male controls. Patients also had low-grade systemic coagulation activation as evidenced by elevated D-dimer, F1 + 2, and PAP plasma levels. Furthermore, similar to sP-selectin and sCD40L antigen, flow cytometric analysis of platelet-derived microparticles in plasma revealed significantly increased numbers in high-TF as compared to low-TF patients and controls. Whereas elevated D-dimer was associated with larger and less differentiated tumors, preoperative plasma TF antigen levels (median [IQR]) were higher in patients with (161 pg/ml [100-236]) than in those without recurrent PC (105 pg/ml [52-182]), as indicated by a serum PSA of >0.1 ng/ml during ambulatory follow-up. In patients with localized PC, preoperative plasma TF antigen levels correlate with platelet activation in vivo and may indicate an increased risk for recurrent disease.

摘要

组织因子(TF)参与癌症的生长和转移,在大多数晚期恶性肿瘤患者中都发现有止血异常,包括前列腺癌(PC)。由于越来越多地筛选抗止血剂延长肿瘤患者生存期的潜力,因此有必要对选定癌症亚型和临床阶段的止血标志物进行详细表征。在本研究中,我们测量了一大群局限性PC患者术前血浆TF抗原,并将其水平与凝血和血小板活化标志物、前列腺特异性抗原(PSA)以及组织病理学结果相关联,以探索其作为该肿瘤实体预后标志物的潜力。在140名患者中,分别有19%和23%的患者血浆TF抗原水平<40 pg/ml(低TF)和>200 pg/ml(高TF),这显著高于42名健康男性对照。患者还存在低度全身凝血活化,表现为D-二聚体、F1 + 2和PAP血浆水平升高。此外,与可溶性P-选择素和可溶性CD40L抗原类似,血浆中血小板衍生微粒的流式细胞术分析显示,与低TF患者和对照相比,高TF患者的数量显著增加。虽然升高的D-二聚体与更大且分化程度更低的肿瘤相关,但术前血浆TF抗原水平(中位数[四分位间距])在有复发性PC的患者(161 pg/ml[100 - 236])中高于无复发性PC的患者(105 pg/ml[52 - 182]),动态随访期间血清PSA>0.1 ng/ml表明了这一点。在局限性PC患者中,术前血浆TF抗原水平与体内血小板活化相关,可能表明复发疾病风险增加。

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