Prognostic and predictive value of intact and cleaved forms of the urokinase plasminogen activator receptor in metastatic prostate cancer

The Prostate ◽  
2010 ◽  
Vol 71 (8) ◽  
pp. 899-907 ◽  
Author(s):  
Charlotte E. Almasi ◽  
Klaus Brasso ◽  
Peter Iversen ◽  
Helle Pappot ◽  
Gunilla Høyer-Hansen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Plasminogen Activator ◽  
Predictive Value ◽  
Metastatic Prostate Cancer ◽  
Urokinase Plasminogen Activator ◽  
Urokinase Plasminogen Activator Receptor ◽  
Plasminogen Activator Receptor

Plasma levels of intact and cleaved urokinase plasminogen activator receptor (uPAR) in men with clinically localised prostate cancer

2017 ◽  
Vol 70 (12) ◽  
pp. 1063-1068
Author(s):  
Gitte Kristensen ◽  
Kasper Drimer Berg ◽  
Solvej Lippert ◽  
Ib Jarle Christensen ◽  
Klaus Brasso ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Plasminogen Activator ◽  
Plasma Levels ◽  
Specific Antigen ◽  
Roc Curves ◽  
Urokinase Plasminogen Activator ◽  
Clinicopathological Parameters ◽  
Prognostic Information ◽  
Urokinase Plasminogen Activator Receptor ◽  
Plasminogen Activator Receptor

AimsLymph node metastasis (N1) is an adverse prognostic factor for men with clinically localised prostate cancer (PCa), but the prediction of N1 disease remains difficult. Urokinase plasminogen activator receptor (uPAR) plays an important role in angiogenesis and tumorigenesis. We analysed whether plasma levels of the soluble uPAR forms uPAR(I-III), uPAR(II-III) and uPAR(I) were associated with the risk of N1 disease in men with clinically localised PCa.MethodsThe present study includes all men (n=518) who underwent radical prostatectomy (RP) for clinically localised PCa, 29 of whom had N1 disease. Soluble uPAR forms were measured using three time-resolved fluorescence immunoassays. The prognostic value of the different uPAR forms together with clinicopathological parameters for N1 disease were analysed using logistic regression, receiver operating characteristic (ROC) regression analysis and quantified using the areas under the ROC curve (AUC).ResultsAll soluble uPAR levels were significantly (p=0.03) higher in patients with N1 disease compared with patients with N0/x disease. ROC curves including clinical tumour stage, biopsy Gleason score, prostate-specific antigen and percent positive biopsies had an AUC of 87.7% for prediction of N1 disease. With the addition of uPAR(I) to the model, the AUC increased to 88.4%.ConclusionsAddition of uPAR(I) level to known diagnostic parameters did not increase the prediction of N1 disease following RP in men with clinically localised PCa. Our results indicate that the plasma levels at diagnosis of the different uPAR forms do not hold important predictive or prognostic information in men with clinically localised PCa.

Urokinase plasminogen activator receptor (uPAR) as a novel biomarker in prostate cancer.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 183-183
Author(s):  
Solvej Lippert ◽  
Kasper Drimer Berg ◽  
Peter Iversen ◽  
Gunilla Høyer-Hansen ◽  
Ib Jarle Christensen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Plasminogen Activator ◽  
Urokinase Plasminogen Activator ◽  
Tumor Stage ◽  
Plasma Samples ◽  
Urokinase Plasminogen Activator Receptor ◽  
Time Resolved ◽  
Plasminogen Activator Receptor ◽  
New Biomarkers ◽  
Domain I

183 Background: New biomarkers are warranted to distinguish between indolent and aggressive prostate cancer (PCa). The urokinase plasminogen activator receptor (uPAR) plays an important role in pericellular proteolysis by binding urokinase plasminogen activator (uPA). This is required for degradation of the extracellular matrix and for cancer invasion. In addition to binding uPAR, uPA cleaves uPAR liberating uPAR(I) and uPAR(II-III). Intact, uPAR(I-III), and uPAR(II-III) can be liberated from the cell surface resulting in three different uPAR forms in circulation. The different uPAR forms are strong prognostic markers in several cancers. We measured the uPAR forms in plasma from patients with different stages of PCa. Methods: Between February 1, 2012 and October 1, 2014, 400 patients with PCa (se table) had plasma samples obtained. The levels of intact uPAR [uPAR(I-III)], intact uPAR + cleaved uPAR domains II+III [uPAR(I-III) + uPAR(II-III)], and cleaved uPAR domain I [uPAR(I)] were determined in citrated plasma samples with two-site sandwich time-resolved fluorescence immunoassays (TR-FIAs). Results: Plasma uPAR(I-III) + uPAR(II-III) and uPAR(I) were significantly higher in hormone naïve patients and CRPC patients compared to patients with localized disease (see table). Quantification of intact uPAR(I-III) revealed no significant differences between the three groups. Conclusions: Our findings suggest that uPAR(I-III) + uPAR(II-III) and uPAR(I) are associated with higher tumor stage as well as advanced PCa disease. These associations suggest that uPAR domains in plasma harbour prognostic value for PCa patients. Further studies are warranted to validate the use of uPAR forms as biomarkers for PCa. [Table: see text]

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