ArticleBMC cancer2014
Prognostic impact of urokinase-type plasminogen activator system components in clear cell renal cell carcinoma patients without distant metastasis.
Article in BMC cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 13 citations in OpenAlex.
- Association of SNPs in the PAI1 Gene with Disease Recurrence and Clinical Outcome in Bladder Cancer.International journal of molecular sciences · 2023Article
- Review of Prognostic Expression Markers for Clear Cell Renal Cell Carcinoma.Frontiers in oncology · 2021Review
- Prognostic value of plasminogen activator inhibitor-1 in biomarker exploration using multiplex immunoassay in patients with metastatic renal cell carcinoma treated with axitinib.Health science reports · 2020Article
- Determination of urokinase-type plasminogen activator serum levels in healthy and oncologic cats.Canadian journal of veterinary research = Revue canadienne de recherche veterinaire · 2020Article
- Exploring the MIR143-UPAR Axis for the Inhibition of Human Prostate Cancer Cells In Vitro and In Vivo.Molecular therapy. Nucleic acids · 2019Article
- Expression of microRNA-3133 correlates with the prognosis in patients with clear cell renal cell carcinoma.Medicine · 2019Article
- Diagnostic and prognostic biomarker potential of kallikrein family genes in different cancer types.Oncotarget · 2018Article
- Transforming growth factor-β promotes aggressiveness and invasion of clear cell renal cell carcinoma.Oncotarget · 2016Article
- Oncolytic virotherapy for urological cancers.Nature reviews. Urology · 2016Review
- Tumor Associated Macrophages in Kidney Cancer.Analytical cellular pathology (Amsterdam) · 2016Review
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14 authors at 5 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
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.
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