Prognostic Value of Urokinase Plasminogen Activator and Plasminogen Activator Inhibitor-1 in Renal Cell Cancer

Hofmann, Rainer; Lehmer, A.; Härtung, R.; Robrecth, Cordula; Buresch, Markus; Grothe, Franziska

doi:10.1016/s0022-5347(01)66328-6

Cited by 33 publications

(17 citation statements)

References 15 publications

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“…With regard to uPA and uPAR, the observations in the different studies vary. While Swiercz et al [23] observed significantly elevated uPA levels in the tumour specimens, others found no significant differences between malignant and non-malignant renal tissues [22, 24, 25, 32]. In contrast, in our study uPA protein levels were significantly decreased in ccRCC tissues compared to the corresponding non-malignant specimens.…”

Section: Discussioncontrasting

confidence: 95%

“…Similar positive correlations have in fact been previously reported between uPA, uPAR, and PAI-1 in tumour tissue extracts of RCC patients [24, 25]. Strikingly, significant correlations between antigen levels of these factors in tumour tissues have been also observed in various other types of cancer [33–35].…”

Section: Discussionsupporting

confidence: 82%

“…The reasons for these discrepancies between the different reports remain unclear so far. Hofmann et al [24, 25], who used the same strategy and analysed a similar number of patients as we did, measured comparable uPA levels in the corresponding renal tissue specimens, whereas Span et al [32] obtained a similar trend of uPA levels in malignant and non-malignant renal tissues as in our study, which did not reach statistical significance ( P = 0.081).…”

Section: Discussionsupporting

confidence: 47%

“…Hofmann et al [24, 25], who also measured antigen levels of uPA, uPAR and PAI-1 in renal tissue extracts from RCC patients by ELISA, revealed all three factors as strong and independent predictors for early relapse.…”

Section: Introductionmentioning

confidence: 99%

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

Fuessel

Erdmann

Täubert³

et al. 2014

BMC Cancer

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BackgroundMembers 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.MethodsCorresponding 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.ResultsAntigen 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).ConclusionsHigh levels of uPA and uPAR in tumour tissue extracts are associated with a significantly shorter DSS of ccRCC patients without distant metastases.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-974) contains supplementary material, which is available to authorized users.

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Section: Discussioncontrasting

confidence: 95%

Section: Discussionsupporting

confidence: 82%

Section: Discussionsupporting

confidence: 47%

Section: Introductionmentioning

confidence: 99%

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

Fuessel

Erdmann

Täubert³

et al. 2014

BMC Cancer

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“…Cell-to-cell interaction antigens and adhesion molecules have also been investigated, i. e., the CA50 tumor-associated antigen, CD44 glycoprotein [ 101, and the VLA-4 antigen which is crucial for the hematogenous spread of RCC [I 11. Urokinase-type plasminogen activator and its inhibitor, plasminogen activator inhibitor, have been analyzed for their association with invasion and formation of metastases [12], and Ki-67 antigen has been studied in association with survival [13]. Other proteins have been investigated as potential renal cancer markers but they have been shown to be either nonspecific or insensitive.…”

Section: Introductionmentioning

confidence: 99%

Renal cell carcinoma and normal kidney protein expression

Sarto¹,

et al. 1997

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Renal cell carcinoma (RCC), a human kidney cancer from the proximal tubular epithelium, accounts for about 3% of adult malignancies. Molecular and cytogenetic analysis have highlighted deletions, translocations, or loss of heterozygosity in the 3p21-p26, a putative RCC locus, as well as in 6q, 8p, 9pq, and 14pq. Studies on phenotypic expression of human kidney tissue and on post-translational modifications in RCC have not yet provided a marker for early renal cell carcinoma diagnosis. Current diagnostic methods do not help to detect the tumor before advanced stages. We therefore used two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) to study normal and tumor kidney tissues in ten patients suffering from RCC. A human kidney protein map in the SWISS-2DPAGE database accessible through the ExPASy WWW Molecular Biology Server was established. Of 2789 separated polypeptides, 43 were identified by gel comparison, amino acid analysis, N-terminal sequencing, and/or immunodetection. The comparison between normal and tumor kidney tissues showed four polypeptides to be absent in RCC. One of them was identified as ubiquinol cytochrome c reductase (UQCR), whose locus has elsewhere been tentatively assigned to chromosome 19p12 or chromosome 22. A second polypeptide was identified as mitochondrial NADH-ubiquinone oxido-reductase complex I whose locus is located on chromosome 18p11.2 and chromosome 19q13.3. These result suggest that the lack of UQCR and of mitochondrial NADH-ubiquinone oxidoreductase complex I expression in RCC may be caused by unknown deletions, or by changes in gene transcription or translation. It might indicate that mitochondrial disfunction plays a major role in RCC genesis or evolution.

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Renal‐cell Carcinoma

2014

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A significant problem for clinicians who treat cancer is the application of the known determinants of disease outcome to the individual patient. The clinical course can be affected by the inherent properties of the tumor, the host‐related factors, and the treatment applied. Renal‐cell carcinoma (RCC) has the reputation of an individual unpredictable outcome with rare cases of spontaneous tumor regression and extended survival despite the presence of metastases. This unpredictable outcome is determined by the genotypic biological behavior and the tumor‐host interaction. Refinement of our ability to predict the outcome should facilitate the rational choice of treatment alternatives and provide more reliability in the interaction with the patient. In case of RCC the absence of other effective treatment modalities besides surgery, renders these considerations even more important.

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Prognostic Value of Urokinase Plasminogen Activator and Plasminogen Activator Inhibitor-1 in Renal Cell Cancer

Cited by 33 publications

References 15 publications

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

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

Renal cell carcinoma and normal kidney protein expression

Renal‐cell Carcinoma

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