肿瘤患者凝血及纤溶分子标志物变化
【摘要】 目的 观察恶性肿瘤患者凝血及纤溶分子标志物的变化，以探索其发生、发展与止凝血的关系。方法 用ELISA方法检测25名正常对照，20例子宫肌瘤，91例恶性肿瘤（肺癌21例、食道癌20例、胃癌23例、结直肠癌27例）组织因子（TF）、组织因子途径抑制物（TFPI）、凝血酶-抗凝血酶复合物（TAT）、尿激酶型纤溶酶原激活物（u-PA）、尿激酶型纤溶酶原激活物受体（u-PAR）、纤溶酶-抗纤溶酶复合物（PAP）的血浆含量。结果 各种恶性肿瘤TF、TAT、u-PA、u-PAR、PAP均显著高于正常对照组，TFPI水平与正常对照组之间无统计学差异；手术后恶性肿瘤组TF、TAT、PAP有所下降，但仍高于正常对照组，而u-PA、u-PAR已与正常对照组之间无统计学差异；子宫肌瘤患者的上述指标测得值与正常对照组之间无统计学差异。结论 恶性实体肿瘤，存在着明显的凝血、纤溶激活状态。TF、TAT、u-PA、u-PAR及PAP可以作为良、恶性肿瘤鉴别的辅助指标，u-PA、u-PAR可以作为判断预后的指标。 Variation of coagulation and fibrinolytic molecular markers in tumor patients
WANG Xuefeng ZHAO Weili QU Bin
（Department of Laboratory, Ruijin Hospital Affiliated to Shanghai Second Medical University, Shanghai Institute of Hematology, Shanghai 200025, China）
【Abstract】 Objective To investigate the variation of coagulation and fibrinolytic molecular markers in tumor patients and their relationship with tumor incidence and development. Methods The plasma levels of tissue factor (TF) and its inhibitor (TFPI ), thrombin-antithrombin complex (TAT), urokinase-type plasminogen activator ( u-PA ) and its receptor (u-PAR), as well as plasmin-antiplasmin complex (PAP), were measured using ELISA in 20 patients with hysteromyoma and 91 patients with malignant tumors including lung cancer 21, esophageal cancer 20, gastric cancer 23, and colorectal carcinoma 27.Results The plasma level of TF, TAT, u-PA, u-PAR, and PAP in group of malignant tumor were significantly higher than that of normal controls (P＜0.05～0.01). TF and TAT increased significantly after operation. However, all these parameters did not vary in patients with uterus myoma.Conclusion Activation of coagulation and fibrinolysis existed in patients with malignant tumor. TF, TAT, u-PA and u-PAR might also be clinical useful markers for tumor determination and u-PA and u-PAR for tumor prognosis.
【Key words】 Thrombin;Plasminogen activators;Carcinoma
止凝血异常在肿瘤的浸润、转移过程中起重要作用，二者的关系日益受到人们的重视。我们对部分止凝血分子标志物在肿瘤患者体内变化进行观察，现报道如下。
材料与方法一、材料
正常对照组25名，男15名，女10名，年龄35～70岁，均为本院健康职工中的志愿者，采血前1个月无服药史。患者组子宫肌瘤组 20例，肺癌组 21例，食道癌组 20例，胃癌组 23，结直肠癌组27例。所有病例接受外科手术治疗后肿块均经病理检查证实。
二、方法
1.标本制备：正常对照及患者组术前和术后15 d 清晨空腹采血，经129 mmol/L柠檬酸三钠9∶1抗凝，3 000 r/min离心15 min，取上清血浆置-20℃冰箱待测。
2.测定指标：(1)组织因子（tissue factor，TF）；(2)组织因子途径抑制物（tissue factor pathway nhibi-tor，TFPI）；(3)凝血酶-抗凝血酶复合物（thrombin-antithrombin，TAT）；(4)尿激酶型纤溶酶原激活物（urokinase type plasminogen activator，u-PA）；(5)尿激
表1 恶性肿瘤患者分子标志物的改变
| 组别 | 例数 | TF(ng/L) | TFPI(μg/L) | TAT(μg/L) | u-PA(μg/L) | u-PAR(μg/L) | PAP(μg/L) |
| 正常对照 | 25 | 33±10 | 63±25 | 1.5±0.6 | 0.45±0.16 | 0.31±0.12 | 0.26±0.10 |
| 肺癌术前 | 21 | 60±28** | 76±34 | 5.0±1.8*** | 0.60±0.31* | 0.42±0.15** | 0.57±0.17*** |
| 肺癌术后 | 21 | 43±28 | 67±20 | 4.0±2.0** | 0.34±0.20 | 0.39±0.21 | 0.38±0.17*▲ |
| 食道癌术前 | 20 | 51±33** | 69±20 | 4.2±1.8** | 0.85±0.40* | 0.53±0.41* | 0.53±0.15*** |
| 食道癌术后 | 20 | 41±12**▲ | 73±22 | 2.9±1.0* | 0.57±0.22 | 0.41±0.21 | 0.38±0.16**▲▲▲ |
| 胃癌术前 | 23 | 48±14** | 67±29 | 4.8±2.8*** | 0.63±0.28* | 0.43±0.22* | 0.59±0.15** |
| 胃癌术后 | 23 | 36±7▲▲ | 70±17 | 3.7±1.9** | 0.36±0.17▲▲ | 0.38±0.17 | 0.39±0.17*▲▲▲ |
| 结肠癌术前 | 27 | 45±17** | 58±20 | 3.9±2.4*** | 0.54±0.15* | 0.45±0.29* | 0.35±0.14* |
| 结肠癌术后 | 27 | 32±8 | 59±18 | 3.0±1.2 | 0.43±0.18 | 0.36±0.20 | 0.30±0.16 |
| 子宫肌瘤术前 | 20 | 28±10 | 57±26 | 2.0±0.9 | 0.34±0.19 | 0.22±0.12 | 0.39±0.14 |
