摘要：

The urokinase plasminogen activator (uPA) system comprises the serine protease uPA, its receptor uPAR and two inhibitors PAI-1 and PAI-2.Components of the uPA system have an important role in tumorigenesis, extracellular matrix (ECM) degradation, angiogenesis, as well as in proliferation, migration and adhesion of tumor cells.They are prognostic factors in different types of cancer.However, effects of co-expression of members of the uPA system in soft-tissue sarcoma (STS) patients at the protein level in both tumor tissue and serum and at the RNA level in tumor tissues have not been investigated yet.We examined 82 STS patients for protein levels of uPA, PAI-1and uPAR in tumor tissue and serum by ELISA.In addition 78 patients were studied for the mRNA expression level of uPA, PAI1, uPAR and an uPAR splice variant, uPAR-del4/5 in tumor tissue by qPCR.A significant correlation between high antigen levels of uPA, PAI-1 or uPAR in tumor tissue, and of uPAR in serum, with poor outcome of STS patients was found for the first time.We detected an additive effect of combined uPA, PAI-1 or uPAR levels in tumor tissue extracts with uPAR levels in serum on patients' prognosis.High uPA/uPAR, PAI-1/uPAR and uPAR/uPAR antigen levels in tumor tissue/serum were associated with a 5.9-fold, 5.8-fold and 6.2-fold increased risk of tumor-related death compared with those patients who displayed low levels of the respective marker combination.On the RNA level we observed only in the subgroup of STS patients with complete tumor resection (R0) a correlation between mRNA expression and disease-associated survival.High PAI-1 and uPAR-del4/5 mRNA levels were associated with a distinctly increased risk of tumor-related death (RR =6.55 and RR =6.00, respectively).In addition a combined expression of high PAI-1 and uPAR-del4/5 mRNA expression levels showed a significant, 19-fold increased risk of tumor-related death compared to the low expression group.In summary, expression of members of the uPA system is additively correlated with prognosis of STS patients.Our results suggest that combinations of these biomarkers can identify STS patients with a higher risk of tumor-related death.

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