Abstract 39: Expression of uPA-system members correlate with the clinico-pathological parameters of PCa patients

Abstract

Abstract Background: Members of the urokinase-type plasminogen activator (uPA) system play an important role in tumor progression and angiogenesis in different human malignancies including breast, kidney, colon, stomach and prostate cancer (PCa). The objective of this study was to determine the mRNA expression and protein levels of uPA system components in tissue specimens and serum samples, respectively, from patients with PCa, and to assess their potential association with clinic-pathological parameters and overall survival (OS). Material and methods: mRNA levels of uPA, its receptor (uPAR) and its inhibitor type 1 (PAI-1) were analyzed in corresponding malignant and adjacent non-malignant prostate tissue specimens from 132 PCa patients. Relative mRNA expression levels were determined by quantitative PCR and normalized to the reference gene TATA-box-binding protein. Pre-operative serum samples from 81 of the 132 PCa patients and 36 patients with benign prostatic hyperplasia (BPH) were analyzed for antigen levels of uPA system members by ELISA. Results: mRNA levels of the uPA system components displayed significant correlations with each other in the tumor tissues (uPA vs. uPAR: rs = 0.550; uPA vs. PAI-1: rs = 0.552; uPAR vs. PAI-1: rs = 0.643; all P < 0.001). A significantly decreased uPA mRNA expression in PCa tissue compared to the corresponding non-malignant tissue specimens was detected (data not shown). High mRNA expression of uPA and PAI-1 was significantly associated with a high Gleason score (P = 0.001 and P = 0.007, respectively; Fig. 2). Antigen levels of uPA and soluble uPAR (suPAR) in serum correlated weakly, but significantly, with each other (rs = 0.382, P < 0.001). A significant association was found between elevated suPAR concentrations in serum and poor OS of PCa patients (P = 0.022, log rank test). In multivariate Cox's regression analysis (adj. for age, lymph node status, tumor stage and Gleason sum) a high suPAR level was associated with a 7.12-fold increased risk of death (P=0.027). Conclusion: The observed association of high suPAR levels with poor survival of PCa patients is consistent with published data on patients afflicted with other types of solid cancer and strongly suggests a general prognostic impact of uPAR antigen levels in serum of cancer patients. Citation Format: Omar Al-Janabi, Helge Taubert, Andrea Lohse-Fischer, Michael Fröhner, Sven Wach, Robert Stöhr, Bastian Keck, Max Burger, Wolf Wieland, Kati Erdmann, Manfred P. Wirth, Bernd Wullich, Gustavo Baretton, Viktor Magdolen, Matthias Kotzsch, Susanne Füssel. Expression of uPA-system members correlate with the clinico-pathological parameters of PCa patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 39. doi:10.1158/1538-7445.AM2014-39