Circulating Levels Of Thrombin Activated Fibrinolysis Inhibitor(TAFI) In Gastric Cancer And Their Clinical Significances

BACKGROUND AND OBJECTIVEGastric cancer is one of the most popular malignant tumors in the world, which ranks fourth in the annual number of new cases of cancer, and ranks second in mortality of cancer. Our country has high incidence of gastric cancer, and the morbidity and mortality rates of gastric cancer are higher than that of the world average. The genesis of gastric cancer is a multi-step, multi-factor process. Early gastric cancer is often asymptomatic, or only has some non-specific gastrointestinal symptoms, so it is very difficult to diagnose early gastric cancer with clinical symptoms alone. Some studies have found that there are close relationships between cancer and coagulation-fibrinolytic system, some cancer patients appears hypercoagulable state or thromboembolism at an early stage. In vivo, cancer changes the coagulation-fibrinolytic system through a variety of ways, and this kind of change will contribute to the genesis and development of cancer. Changes in coagulation and fibrinolysis systems of patients with malignant tumors, and their thrombotic complications become a hot research in home and abroad in recent years.Thrombin activated fibrinolysis inhibitor (TAFI) is mainly synthesized and secreted by the liver, which is a kind of single-chain glycoprotein with plasma carboxypeptidase activity and exists in plasma in a zymogen form. TAFI can be actived by trypsin, plasmin, thrombin, thrombomodulin (TM) and other enzymes, TAFI is hydrolyzed to remove the peptide chain of92amino acid residues, and changed into its activated form TAFIa. TAFIa hydrolyzes the C-terminal lysine residues of fibrin, thereby inhibiting the conversion of plasminogen to plasmin, play the role of indirect antifibrinolytic. TAFIa can also directly inhibit the activity of plasminogen to play a direct role in inhibition of fibrinolysis. Thus, TAFI plays an important role in the balance of coagulation and fibrinolysis. Antithrombin is the body’s most important cytokine, which plays a role in anticoagulation; thrombin-antithrombin complex is the complex of antithrombin and thrombin.In this study, we chose patients with gastric cancer, patients with benign gastric disease and health individuals from Second Hospital of Shandong University as subjects. We measured the plasma levels of TAFI, thrombin-antithrombin complex (TAT), D-dimer and fibrinogen of those individuals, analyzed their differences and explored the relationships between TAFI and TAT levels and gastric cancer.METHODS48cases of gastric cancer and34cases of benign gastric disease patients were collected from Second Hospital of Shandong University, and50healthy individuals were enrolled as normal controls. We used a chromogenie substrate method to measure the plasma level of TAFI, an ELIS A method to measure the level of TAT. The levels of D-dimer and fibrinogen were measured by latex enhanced turbidimetric immunoassay and Clauss assay, respectively. We analyzed the changes of these indicators of in different groups. The best diagnostic value and the power of test of TAT and TAFI were evaluated by receiver operating characteristic curve (ROC curve).RESULTSThe level of TAFI in gastric cancer was30.6±6.6μg/mL, higher than that in benign gastric disease group (24.3±5.4μg/mL) and healthy control group (22.8±5.1μg/mL), the difference was statistically significant (P<0.05); the level of TAT in gastric cancer was41.0±12.2ng/mL, higher than that in benign gastric disease group (27.0±8.0ng/mL) and healthy control group (24.9±8.0ng/mL), the difference was statistically significant (P<0.05). Meanwhile, levels of D-dimer and fibrinogen in gastric cancer were significantly higher (P<0.05); while compared the healthy control group and benign gastric disease group, the difference was not statistically significant of the above four indicators (P>0.05). When the cutoff of TAFI was28.85μg/mL, the sensitivity and specificity of the test was0.646and0.869, respectively; when the cutoff of TAT was31.50ng/mL, the sensitivity and specificity of the test was0.813and0.786respectively.CONCLUSIONSCompared with control groups, the levels of TAFI were significantly higher in patients with gastric cancer, indicating that patients with gastric cancer had some changes in coagulation and fibrinolytic system, and a tendency to thrombosis; TAFI is expected to be a predictor of the risk of gastric cancer.