title: Heparanase procoagulant activity is elevated and predicts survival in non-small cell lung cancer patients.
abstract: BACKGROUND
  Heparanase is implicated in angiogenesis and tumor progression. We had earlier demonstrated that heparanase may also affect the hemostatic system in a non-enzymatic manner. It forms a complex and enhances the activity of the blood coagulation initiator- tissue factor (TF). Although increased heparanase antigen level in the plasma and biopsies of cancer patients was previously demonstrated, in the present study we evaluated, for the first time, the heparanase procoagulant activity in the plasma of patients with lung cancer.
  
  
  METHODS
  Sixty five patients with non-small cell lung cancer at presentation and twenty controls were recruited. Plasma was studied for TF / heparanase procoagulant activity, TF activity and heparanase procoagulant activity using chromogenic assay and heparanase antigen levels by ELISA.
  
  
  RESULTS
  Heparanase antigen levels were higher in the study group compared to control (P=0.05). TF / heparanase activity, and even more apparent, heparanase procoagulant activity were significantly higher in the study group compared to controls (P=0.008, P<0.0001, respectively). No significant difference was observed in the TF activity between the groups. Survival of patients with heparanase procoagulant activity higher than 31 ng/ml predicted a mean survival of 9 ± 1.3 months while heparanase procoagulant activity of 31 ng/ml or lower predicted a mean survival of 24 ± 4 months (P=0.001). Heparanase procoagulant activity was higher than 31 ng/ml in the four cases of thrombosis detected during the follow-up period.
  
  
  CONCLUSIONS
  Elevated heparanase procoagulant activity in patients with lung cancer reveals a new mechanism of coagulation system activation in malignancy. Heparanase procoagulant activity can potentially be used as a predictor for survival.
authors: Thrombosis and Hemostasis Unit, Rambam Health Care Campus, The Bruce Rappaport Faculty of Medicine, Technion Haifa, Israel. Electronic address: ynadir@netvision.net.il.
authors: Y
authors: Y
authors: Nadir
authors: Thrombosis and Hemostasis Unit, Rambam Health Care Campus, The Bruce Rappaport Faculty of Medicine, Technion Haifa, Israel.
authors: G
authors: G
authors: Sarig
authors: Thrombosis and Hemostasis Unit, Rambam Health Care Campus, The Bruce Rappaport Faculty of Medicine, Technion Haifa, Israel.
authors: E
authors: E
authors: Axelman
authors: Division of Oncology, Rambam Medical Centre, The Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel.
authors: A
authors: A
authors: Meir
authors: Division of Oncology, Rambam Medical Centre, The Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel.
authors: M
authors: M
authors: Wollner
authors: Cancer and Vascular Biology Research Center, The Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel.
authors: I
authors: I
authors: Shafat
authors: Thrombosis and Hemostasis Unit, Rambam Health Care Campus, The Bruce Rappaport Faculty of Medicine, Technion Haifa, Israel.
authors: R
authors: R
authors: Hoffman
authors: Thrombosis and Hemostasis Unit, Rambam Health Care Campus, The Bruce Rappaport Faculty of Medicine, Technion Haifa, Israel.
authors: B
authors: B
authors: Brenner
authors: Cancer and Vascular Biology Research Center, The Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel.
authors: I
authors: I
authors: Vlodavsky
authors: Division of Oncology, Rambam Medical Centre, The Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel.
authors: N
authors: N
authors: Haim
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D001777:Blood Coagulation; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000150:complications / Q000201:enzymology* / Q000401:mortality; D016022:Case-Control Studies; D005260:Female; D005966:Glucuronidase / Q000097:blood*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000097:blood / Q000150:complications / Q000201:enzymology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors; D013927:Thrombosis / Q000097:blood / Q000201:enzymology / Q000209:etiology; D013997:Time Factors; D015854:Up-Regulation; D000099175:Heparanase
chemical_list: D014408:Biomarkers, Tumor; D005966:Glucuronidase; D000099175:Heparanase
keywords: Coagulation; Heparanase; Lung cancer; Prognosis