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Prognostic impact of urokinase-type plasminogen activator system components in clear cell renal cell carcinoma patients without distant metastasis - PubMed

  • ️Wed Jan 01 2014

Prognostic impact of urokinase-type plasminogen activator system components in clear cell renal cell carcinoma patients without distant metastasis

Susanne Fuessel et al. BMC Cancer. 2014.

Abstract

Background: Members of the urokinase-type plasminogen activator (uPA) system including uPA, its receptor uPAR and the plasminogen activator inhibitor 1 (PAI-1) play an important role in tumour invasion and progression in a variety of tumour types. Since the majority of clear cell renal cell carcinoma (ccRCC) shows distant metastasis at time of diagnosis or later, the interplay of uPA, uPAR and PAI-1 might be of importance in this process determining the patients' outcome.

Methods: Corresponding pairs of malignant and non-malignant renal tissue specimens were obtained from 112 ccRCC patients without distant metastasis who underwent tumour nephrectomy. Tissue extracts prepared from fresh-frozen tissue samples by detergent extraction were used for the determination of antigen levels of uPA, uPAR and PAI-1 by ELISA. Antigen levels were normalised to protein concentrations and expressed as ng per mg of total protein.

Results: Antigen levels of uPA, uPAR, and PAI-1 correlated with each other in the malignant tissue specimens (rs=0.51-0.65; all P<0.001). Antigen levels of uPA system components were significantly higher in tissue extracts of non-organ confined tumours (pT3+4) compared to organ-confined tumours (pT1+2; all P<0.05). Significantly elevated levels of uPAR and PAI-1 were also observed in high grade ccRCC. When using median antigen levels as cut-off points, all three uPA system factors were significant predictors for disease-specific survival (DSS) in univariate Cox's regression analyses. High levels of uPA and uPAR remained independent predictors for DSS with HR=2.86 (95% CI 1.07-7.67, P=0.037) and HR=4.70 (95% CI 1.51-14.6, P=0.008), respectively, in multivariate Cox's regression analyses. A combination of high antigen levels of uPA and/or uPAR further improved the prediction of DSS in multivariate analysis (HR=14.5, 95% CI 1.88-111.1, P=0.010). Moreover, high uPA and/or uPAR levels defined a patient subgroup of high risk for tumour-related death in ccRCC patients with organ-confined disease (pT1+2) (HR=9.83, 95% CI 1.21-79.6, P=0.032).

Conclusions: High levels of uPA and uPAR in tumour tissue extracts are associated with a significantly shorter DSS of ccRCC patients without distant metastases.

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Figures

Figure 1
Figure 1

Protein levels in matched pairs of malignant and non-malignant renal tissue specimens. Distribution of protein levels of A) uPA, B) uPAR and C) PAI-1 in malignant (Tu) and non-malignant (Tf) renal tissues from 112 ccRCC patients assessed by ELISA is presented by boxplots. The boxes represent the 25th – 75th percentiles, the whiskers indicate the 10th and 90th percentiles. The median values are depicted as solid lines within the boxes. The Wilcoxon test was used to test for significant differences in antigen levels between Tu and Tf.

Figure 2
Figure 2

Disease-specific survival of the ccRCC patients in relation to the uPA system components. Kaplan-Meier curves show the dependence of disease-specific survival (DSS) on the protein levels of A) uPA, B) uPAR and C) PAI-1. Differences in DSS between patients with low and high levels of the uPA system components were assessed using the log-rank test.

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Pre-publication history
    1. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/14/974/prepub

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