Abstract
4766 Background: Plasminogen system plays a significant role in cancer cell invasion and metastasis. Elevated tumor urokinase plasminogen activator (uPA), its receptor- uPAR, and inhibitor, plasminogen activator inhibitor (PAI-1) levels are associated with poor prognosis in several cancers (Manders et al. Cancer 2004, Duffy MJ. Clin Biochem 2004).We conducted two preliminary studies to evaluate its prognostic significance in advanced prostate cancer. Methods: In the first study fresh tissue from patients with local stage (n=9 prostatectomy specimens) and advanced stage (n=6 transurethral prostate resections) was collected. uPA and plasminogen (PLG) mRNA expression was evaluated by real-time polymerase chain reaction. Transcript abundance was normalized to 18s (control) and t-test used for detecting differences between means of both groups. In a second study plasma uPA, uPAR and PAI-1 levels were measured in advanced stage patients (pts) undergoing androgen deprivation (n=40) who were followed for overall and progression free survival (PFS). Mean values of all variables with and without progression were compared and univariate Cox proportional hazard ratios (HR) calculated. Results: uPA and PLG gene expression was found in all fresh tumor specimens (table). Elevated expression was observed in advanced stage specimens. In the second study 25/40 pts were found to have events (radiological progression) after a median follow up of 36.1 months, of these 17 have died. Prognostically only elevated uPAR levels were found to be statistically significant for PFS. Mean uPAR in pts with events versus without events was 11.04 vs 17.89 ng/ml (HR= 0.75, p= 0.028). Conclusions:This is the first analysis evaluating the role for the plasminogen system in advanced prostate cancer. Elevated uPAR was associated with 25% increase in PFS. We propose a prospective study of various plasminogen system proteases in advanced prostate cancer to better define its impact on survival. No significant financial relationships to disclose.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
