肺癌患者血栓前状态分子标志物的检测及意义

Clinical Significance of Detecting Plasma Biomarkers of Prethrombotic State in Lung Cancer Patients

目的观察肺癌患者血浆中血栓前状态分子标志物的变化,并探讨其临床意义。方法选取2010年6月至2012年6月住院确诊的肺癌患者90例(肺癌组),健康志愿者90例(对照组)。采用ELISA法检测肺癌患者及健康志愿者血浆中人血管性血友病因子(vWF)、人P-选择素和人凝血酶抗凝血酶复合物的含量;采用ACLTOP全自动凝血分析仪检测凝血全套指标,其中血浆凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(FIB)的血浆含量采用凝固法检测,血浆D-二聚体浓度的测定采用免疫比浊法,抗凝血酶Ⅲ(AT-Ⅲ)的测定采用底物发光法。结果肺癌组血浆vWF、P-选择素、TAT、D-二聚体、FIB水平均较对照组明显增高(P<0.05),AT-Ⅲ、APTT均较对照组显著降低或缩短(P<0.05),而PT与对照组比较差异无统计学意义(P>0.05)。Ⅳ期肺癌患者的血浆vWF、P-选择素、TAT、FIB、D-二聚体水平均显著高于Ⅲ期及Ⅰ+Ⅱ期肺癌患者(P<0.05)。Ⅳ期肺癌患者的血浆PT及APTT均较Ⅲ期及Ⅰ+Ⅱ期肺癌患者明显缩短(P<0.05),且Ⅳ期肺癌患者的AT-Ⅲ活性也较Ⅲ期及Ⅰ+Ⅱ期明显降低(P<0.05)。结论肺癌患者存在明显的血栓前状态,且AT-Ⅲ、vWF、D-二聚体、FIB、TAT、P-选择素以及APTT是早期诊断血栓前状态的可靠标志物,其中以vWF、TAT、P-选择素以及D-二聚体的敏感性和特异性较高。

Objective To explore the clinical significance of plasma biomarkers of prethrombotic state in lung cancer patients. Methods 90 patients with lung cancer （lung cancer group） and 90 normal controls （control group） of Han population in Shanghai Pulmonary Hospital from June 2010 to June 2012 were recruited in the study. Enzyme-linked immunosorbent assay （ELISA） was used to detect the plasma levels of von willebrand factor（vWF） ,P-selectin,and thrombin-antithrombine complex （TAT）. Coagulation indicators were detected by ACLTOP full automatic coagulation analyzer. Solidification method was used to detect the plasma levels of prothrombin time （ PT）, activated partial thromboplastin time （AFIT） and fibrinogen （FIB）. Turbidimetric immunoassay was used to detect D-dimer concentration, and chemiluminescence substrate was used to assay antithrombin Ⅲ（ AT-Ⅲ ）. Results In the lung cancer group, the plasma levels of vWF, P-selectin, TAT, D-dimer and FIB were significantly higher than those in the control group （P 〈 0.05 ）, and the plasma levels of APTT and AT- Ⅲ were lower than those in the control group（P 〈0. 05） ,while there was no significant difference in plasma PT level（P 〉0. 05）. In stage IV lung cancer subgroup, the plasma levels of vWF, P-selectin, TAT, D-dimer and FIB were significantly higher than those in the stage Ⅲ subgroup or the stageⅠ ＋ Ⅱ subgroup （P 〈 0. 05）. And the plasma levels of PT and AFIT were significantly lower than those in the stage Ⅲ subgroup or the stage Ⅰ ＋ Ⅱ subgroup （ P 〈 0. 05）. Conclusions The patients with lung cancer exist obvious prethrombotic state. AT-Ⅲ, vWF, D-dimer, FIB, TAT, P-selectin and APTY can be used as reliable hematol markers in early diagnosis of prethrombotic state, vWF,P-selectin,TAT and D-dimer have higher sensitivity and specificity.