Clinical evaluation of thrombus molecular markers in patients with malignant tumor

Q4 Health Professions

中华检验医学杂志 Pub Date : 2020-01-11 DOI:10.3760/CMA.J.ISSN.1009-8158.2020.01.009

Yangyang Zheng, Hairun Yan, Qi Li, H-G Ji, Zheng-bing Yang, Qinzhen Zhang

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Abstract

Objective To explore the early diagnostic value of thrombus molecular markers in thrombosis ofpatients with malignant tumors and to evaluate their risk factors. Methods Diagnostic research.A total of 1366 patients (including lung cancer, breast cancer and colorectal cancer,) were randomly selected in the Red Flag Hospital of Mudanjiang Medical College and Mudanjiang Cancer Hospitalfrom September 2009 to February 1919. Among them, 562 were males and 804 were females with average age (59.45±15.10) years old. The control group consisted of 70healthy donors (35 males and 35 females, with an average age of (49.60±19.12) years old), including 69 cases of venous thrombosis (thrombotic group, 32 males and37 females, with an average age of (61.20±15.71) years old).Chemoluminescent enzyme immunoassay was used to detect thromboregulatory proteins(TM), thrombin-antithrombin complexes(TAT), tissue plasminogen activators/inhibitors -1 complexes(t-PAIC), plasminase-anti-fibrinolysis complexes(PIC) in venous plasma. According to the sensitivity and specificity of each marker, the receiver′s work characteristic curve was drawn to evaluate its diagnostic performance. Cox regression analysis was used for single-factor and multi-factor risk analysis. Results The incidence of venous thromboembolism(VTE) in patients with different types of malignant tumors was statistically significant, with lung cancer being the highest, followed by colorectal cancer and breast cancer(P<0.05). The levels of TM, TAT, t-PAIC and PIC were significantly higher in the lung, breast and colorectal thrombosis group than in the control group. The differences were statistically significant(all P<0.05). The optimal cut-off level for TM is 10.57 IU/ml(sensitivity 50.30%, specificity 75.50%, AUC=0.671), and the optimal cut-off level for TAT is 4.16 ng/ml(sensitivity is 80.30%, specificity is 62.80%, AUC=0.757).The optimal truncation level for t-PAIC is 11.44 ng/ml(sensitivity 52.50%, specificity 84.00%, AUC=0.682), and the optimal truncation level for PIC is 1.18μg/ml(sensitivity 67.20%, specificity is 79.50%, AUC=0.790). The combined detection of the four molecular markers has the best sensitivity and diagnostic performance(86.90%, AUC=0.807). Age, stage, metastasis, surgery, tumor diameter, and PIC levels are independent factors that affect the occurrence of VTE in malignant tumors (all P<0.05). Conclusions Different types of malignant tumors have different rates of thrombosis. The combined detection ofTM, TAT, t-PAIC and PIC have the best diagnostic performance, and can be used as a new early diagnosis method for VTE in malignant tumors. Age, stage, metastasis, surgery, and tumor diameter are risk factors for VTE in malignant tumors. PIC levels can be used as a reliable markerfor the risk of VTE in patients with malignant tumors within 6 months. Key words: Neoplasms; Venous thromboembolism; Biomarkers

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恶性肿瘤患者血栓分子标志物的临床评价

目的探讨血栓分子标志物在恶性肿瘤患者血栓形成中的早期诊断价值，并评价其危险因素。方法诊断研究。随机选取牡丹江医学院红旗医院和牡丹江肿瘤医院2009年9月至1919年2月期间的肺癌、乳腺癌和结直肠癌患者1366例。其中男性562例，女性804例，平均年龄(59.45±15.10)岁。对照组为健康献血者70例(男35例，女35例，平均年龄(49.60±19.12)岁)，其中静脉血栓69例(血栓组男32例，女37例，平均年龄(61.20±15.71)岁)。采用化学发光酶免疫分析法检测静脉血浆中的血栓调节蛋白(TM)、凝血酶-抗凝血酶复合物(TAT)、组织型纤溶酶原激活物/抑制剂-1复合物(t- pai)、纤溶酶-抗纤溶复合物(PIC)。根据各标志物的敏感性和特异性，绘制受者工作特征曲线，评价其诊断效能。单因素和多因素风险分析采用Cox回归分析。结果静脉血栓栓塞(venous thromboembolism, VTE)在不同类型恶性肿瘤患者中的发生率均有统计学意义，以肺癌最高，其次为结直肠癌和乳腺癌(P<0.05)。肺、乳腺、结直肠血栓组TM、TAT、t- pac、PIC水平均显著高于对照组。差异均有统计学意义(P<0.05)。TM的最佳临界值为10.57 IU/ml(灵敏度为50.30%，特异性为75.50%，AUC=0.671)， TAT的最佳临界值为4.16 ng/ml(灵敏度为80.30%，特异性为62.80%，AUC=0.757)。t- pac的最佳截断水平为11.44 ng/ml(灵敏度52.50%，特异度84.00%，AUC=0.682)， PIC的最佳截断水平为1.18μg/ml(灵敏度67.20%，特异度79.50%，AUC=0.790)。4种分子标记联合检测具有最佳的灵敏度和诊断性能(86.90%，AUC=0.807)。年龄、分期、转移、手术、肿瘤直径、PIC水平是影响恶性肿瘤VTE发生的独立因素(均P<0.05)。结论不同类型恶性肿瘤的血栓形成率不同。tm、TAT、t- pac和PIC联合检测诊断效果最好，可作为恶性肿瘤静脉血栓栓塞的一种新的早期诊断方法。年龄、分期、转移、手术和肿瘤直径是恶性肿瘤发生静脉血栓栓塞的危险因素。PIC水平可作为恶性肿瘤患者6个月内静脉血栓栓塞风险的可靠指标。关键词:肿瘤;静脉血栓栓塞;生物标记物

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