紫杉醇联合卡铂化疗对卵巢癌凝血/纤溶及CA125/HE4水平的调控及临床意义

Regulation and clinical significance of paclitaxel with carboplatin combined chemotherapy on coagulation/fibrinolysis and CA125/HE4 levels in ovarian cancer

目的:探讨紫杉醇联合卡铂联合化疗对卵巢癌(OC)凝血/纤溶及肿瘤标志物的影响及临床意义。方法:研究分为OC联合化疗(CC)和良性卵巢肿瘤对照(control)组,各组50例。借助苏木精-伊红(HE)染色和透射电镜(TEM)观察卵巢病理学改变;采用全自动凝血分析仪及凝固法检测凝血酶原时间(PT-SEC)、凝血酶原国际标准比值(PT-INR)、凝血酶原时间比值(PT-RATIO)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)、纤维蛋白原(FIB)及抗凝血酶-Ⅲ(AT-Ⅲ)水平;免疫比浊法测定纤维蛋白(原)降解产物(FDP)和D-二聚体(D-D)含量;采用电化学发光法检测糖类抗原125(CA125)和人附睾蛋白4(HE4)水平;并绘制受试者工作特征(ROC)曲线,以分析凝血/纤溶产物与肿瘤标志物的相关性。结果:光镜显示卵巢浆液性癌(SC)细胞坏死和腺腔样结构,超微结构显示线粒体显著肿胀和嵴溶解,联合化疗后卵巢SC呈现正常线粒体与“脂质空泡”并存的现象。凝血与纤溶指标检测显示,OC患者化疗前TT和AT-Ⅲ水平显著降低(P<0.01),APTT、FIB、FDP、D-D、CA125和HE4水平均高于对照组(P<0.05);化疗后TT和AT-Ⅲ水平显著升高(P<0.01),其他指标均显著降低(P<0.01)。ROC曲线分析显示肿瘤标志物和纤溶产物对OC具有诊断价值。结论:联合化疗对OC患者凝血与纤溶功能具有调节作用,其纤溶产物与肿瘤标志物的消长变化对OC的预测和干预评估具有诊断价值。

AIM To investigate the effect and clinical significance of paclitaxel with carboplatin combined chemotherapy on coagulation/fibrinolysis and tumor markers of ovarian cancer(OC).METHODS The study was divided into OC combined chemotherapy(CC)and benign ovarian tumor control group with 50 cases in each group.The pathological changes of ovary were observed by hematoxylin-eosin(HE)staining and transmission electron microscope(TEM).The levels of prothrombin time(PT-SEC),prothrombin international standard ratio(PT-INR),prothrombin time ratio(PT-RATIO),activated partial thrombin time(APTT),thrombin time(TT),fibrinogen(FIB)and antithrombin-Ⅲ(AT-Ⅲ)were measured by automatic coagulation analyzer and coagulation method.Fibrin(gen)degradation products(FDP)and D-dimer(D-D)were determined by immunoturbidimetric method.The levels of carbohydrate antigen 125(CA125)and human epididymal protein 4(HE4)were detected by electrochemiluminescence.Receiver operating characteristic(ROC)curves were plotted to analyze the correlation between coagulation/fibrinolysis products and tumor markers.RESULTS Light microscopy showed cell necrosis and adenoid structure in ovarian serous carcinoma(SC).Ultrastructure observation showed obvious mitochondrial swelling and ridge dissolution.After combined chemotherapy,the ovarian SC showed the coexistence of normal mitochondria and lipid vacuole.The levels of TT and AT-Ⅲwere significantly decreased in OC patients before chemotherapy(P<0.01),and the levels of APTT,FIB,FDP,D-D,CA125 and HE4 were higher than those in control group(P<0.05).However,the levels of TT and AT-Ⅲwere significantly increased(P<0.01),and the other indexes were significantly lower than those of control group after chemotherapy(P<0.01).ROC curve analysis showed that tumor markers and fibrinolysis products had diagnostic value for OC.CONCLUSION Combined chemotherapy can regulate coagulation and fibrinolytic function in patients with OC,and the fluctuation of serum fibrinolytic products and tumor markers has diagnostic value for the prediction and intervention evaluation of OC.