Tissue Factor Pathway Inhibitor 2: A Novel Biomarker for Predicting Asymptomatic Venous Thromboembolism in Patients with Epithelial Ovarian Cancer
Tissue Factor Pathway Inhibitor 2: A Novel Biomarker for Predicting Asymptomatic Venous Thromboembolism in Patients with Epithelial Ovarian Cancer
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DOI：
10.1159/000524804
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发表时间：
2022-05-25
影响因子：
2.1
通讯作者：
Kobayashi，Hiroshi
中科院分区：
文献类型：
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作者：
Yamanaka，Shoichiro;Miyake，Ryuta;Kobayashi，Hiroshi
目的无症状静脉血栓栓塞症(VTE)患者与肺血栓栓塞症事件的风险增加相关。然而，由于D-二聚体检测的特异性低，假阳性率高，不能单独使用D-二聚体检测来诊断VTE。组织因子途径抑制物2(TFPI2)是一种新的卵巢癌血清学标志物，在凝血系统调节中起重要作用。我们推测D-二聚体和TFPI2联合应用将提高其在诊断VTE中的作用。本研究旨在探讨血清D-二聚体和TFPI2水平在检测上皮性卵巢癌(EOC)患者无症状VTE中的临床应用价值。设计2008年1月至2015年12月，奈良医科大学医院妇科的研究人员进行了一项单中心回顾性研究。应用受试者工作特征(ROC)曲线分析确定D-二聚体、TFPI2及D-二聚体与TFPI2联合检测对VTE患者与非VTE患者的诊断价值。结果静脉血栓栓塞组与非静脉血栓栓塞组患者血浆D-二聚体、TFPI2、CA125水平及肿瘤残留率差异均有统计学意义。D-二聚体水平与年龄、体重指数、静脉曲张、大量腹水、残留肿瘤、组织学、妇产科联合分期显著相关，而TFPI2仅与静脉曲张有关。多因素分析显示，D-二聚体(最佳临界值为3.5pg/m L)和TFP I_2(最佳临界值为400pg/m L)是术前静脉血栓栓塞术前的独立危险因素。ROC分析显示，D-二聚体的曲线下面积为0.8266，TFPI2的曲线下面积为0.7963，D-二聚体和TFPI2的结合曲线下面积为0.8495。与D-二聚体单独检测相比，D-二聚体和TFPI2联合检测对VTE的诊断具有更高的特异性(77.3-96.9%)和阳性预测值(48.8-81.2%)。
ObjectivesPatients with asymptomatic venous thromboembolism (VTE) are associated with an increased risk of pulmonary thromboembolism events. However, due to low specificity and high false-positive rates, D-dimer testing cannot be used alone to diagnose VTE. Tissue factor pathway inhibitor 2 (TFPI2), a new serodiagnostic marker for ovarian cancer, plays a role in blood coagulation system regulation. We hypothesized that combining D-dimer and TFPI2 would improve its utility in diagnosing VTE. This study aimed to look into the clinical utility of serum D-dimer and TFPI2 levels in detecting asymptomatic VTE in patients with epithelial ovarian cancer (EOC).DesignFrom January 2008 to December 2015, researchers at Nara Medical University Hospital’s Department of Gynecology conducted a single-center retrospective study. The receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic value of preoperative D-dimer, TFPI2, and D-dimer combined with TFPI2 in distinguishing VTE patients from those who did not have VTE.ParticipantsThis study included 122 patients with EOC who met the inclusion and exclusion criteria out of 223 admitted to the hospital with EOC. The patients were divided into two groups: VTE (n= 25) and non-VTE (n= 97).ResultsThere were significant differences in D-dimer, TFPI2, and CA125 levels and residual tumor between the VTE and non-VTE groups. The D-dimer level was found to be significantly related to age, body mass index, VTE, massive ascites, residual tumor, histology, and Federation of Gynecology and Obstetrics stage, whereas the TFPI2 level was only related to VTE. Multivariate analysis revealed that D-dimer (the optimal cutoff value, 3.5 μg/mL) and TFPI2 (the optimal cutoff value, 400 pg/mL) are independent risk factors for preoperative VTE. ROC analysis revealed that the area under the curve was 0.8266 for D-dimer, 0.7963 for TFPI2, and 0.8495 for the combination of D-dimer and TFPI2. When compared to the D-dimer test alone, the combination of D-dimer and TFPI2 had higher specificity (77.3–96.9%) and positive predictive value (48.8–81.2%) for the diagnosis of VTE.LimitationsThis is a single-center retrospective study.ConclusionThe combination of D-dimer and TFPI2 may be useful to safely exclude VTE and select patients at high risk of VTE.