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

被引：11

作者：

Fuessel S. ^{[1
]}

Erdmann K. ^{[1
]}

Taubert H. ^{[2
]}

Lohse-Fischer A. ^{[1
]}

Zastrow S. ^{[1
]}

Meinhardt M. ^{[3
]}

Bluemke K. ^{[4
]}

Hofbauer L. ^{[5
]}

Fornara P. ^{[6
]}

Wullich B. ^{[2
]}

Baretton G. ^{[3
]}

Magdolen V. ^{[7
]}

Wirth M.P. ^{[1
]}

Kotzsch M. ^{[3
]}

机构：

[1] Department of Urology, Technische Universität Dresden, Fetscherstrasse 74, Dresden

[2] Department of Urology, Universität Erlangen, Hartmannstrasse 14, Erlangen

[3] Institute of Pathology, Technische Universität Dresden, Fetscherstrasse 74, Dresden

[4] Institute of Legal Medicine, Martin Luther Universität Halle-Wittenberg, Franzosenweg 1, Halle

[5] Department of Medicine III, Technische Universität Dresden, Fetscherstrasse 74, Dresden

[6] Department of Urology, Martin Luther Universität Halle-Wittenberg, Ernst-Grube-Strasse 40, Halle

[7] Technische Universität München, Clinical Research Unit, Department of Obstetrics and Gynecology, Ismaninger Strasse 22, München

来源：

BMC Cancer | / 14卷 / 1期

关键词：

PAI-1; Prognostic biomarker; Renal cell carcinoma; uPA; uPA system; uPAR;

D O I：

10.1186/1471-2407-14-974

中图分类号：

学科分类号：

摘要：

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. © 2014 Fuessel et al.

引用

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