Combined mRNA expression levels of members of the urokinase plasminogen activator (uPA) system correlate with disease-associated survival of soft-tissue sarcoma patients
1 Institute of Pathology, Dresden University of Technology, Dresden, Germany
2 Department of Obstetrics and Gynecology, Technical University of Munich, München, Germany
3 Center for Reproductive Medicine and Andrology, Martin-Luther-University Halle-Wittenberg, Halle, Germany
4 Department of Oral and Maxillofacial Plastic Surgery, Martin-Luther-University Halle-Wittenberg, Halle, Germany
5 Department of Radiotherapy, Martin-Luther-University Halle-Wittenberg, Halle, Germany
6 Institute of Medical Biometry and Informatics, Martin-Luther-University Halle-Wittenberg, Halle, Germany
7 Department of Urology, Dresden University of Technology, Dresden, Germany
8 Medical Laboratory Unit, Bautzen, Germany
9 Department of General and Oncological Surgery, Clinical Unit Bremen-Mitte, Bremen, Germany
10 Klinik für Urologie, Universitätsklinikum und Nikolaus-Fiebiger-Zentrum für Molekulare Medizin der Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany
BMC Cancer 2011, 11:273 doi:10.1186/1471-2407-11-273Published: 25 June 2011
Members of the urokinase-type plasminogen activator (uPA) system are up-regulated in various solid malignant tumors. High antigen levels of uPA, its inhibitor PAI-1 and its receptor uPAR have recently been shown to be associated with poor prognosis in soft-tissue sarcoma (STS) patients. However, the mRNA expression of uPA system components has not yet been comprehensively investigated in STS patients.
The mRNA expression level of uPA, PAI-1, uPAR and an uPAR splice variant, uPAR-del4/5, was analyzed in tumor tissue from 78 STS patients by quantitative PCR.
Elevated mRNA expression levels of PAI-1 and uPAR-del4/5 were significantly associated with clinical parameters such as histological subtype (P = 0.037 and P < 0.001, respectively) and higher tumor grade (P = 0.017 and P = 0.003, respectively). In addition, high uPAR-del4/5 mRNA values were significantly related to higher tumor stage of STS patients (P = 0.031). On the other hand, mRNA expression of uPA system components was not significantly associated with patients' survival. However, in STS patients with complete tumor resection (R0), high PAI-1 and uPAR-del4/5 mRNA levels were associated with a distinctly increased risk of tumor-related death (RR = 6.55, P = 0.054 and RR = 6.00, P = 0.088, respectively). Strikingly, R0 patients with both high PAI-1 and uPAR-del4/5 mRNA expression levels showed a significant, 19-fold increased risk of tumor-related death (P = 0.044) compared to the low expression group.
Our results suggest that PAI-1 and uPAR-del4/5 mRNA levels may add prognostic information in STS patients with R0 status and distinguish a subgroup of R0 patients with low PAI-1 and/or low uPAR-del4/5 values who have a better outcome compared to patients with high marker levels.