Prognostic relevance of uPAR-del4/5 and TIMP-3 mRNA expression levels in breast cancer
Abstract
Recently, two components of important protease systems in cancer, i.e., the urokinase plasminogen activator receptor (uPAR) mRNA splice variant uPAR-del4/5 and the tissue inhibitor of matrix metalloproteinase-3 (TIMP-3), were independently reported to be of prognostic value in breast cancer. In the present study, we have evaluated the impact of both these factors on disease-free survival (DFS) in 205 breast cancer patients by assessing mRNA expression in tumour tissue by quantitative PCR. High uPAR-del4/5 mRNA expression was associated with shorter DFS in breast cancer patients (P=0.0363), whereas high TIMP-3 mRNA levels were associated with a good prognosis (P=0.0049). Furthermore, by combining uPAR-del4/5 with TIMP-3 values, we demonstrate that breast cancer patients with high uPAR-del4/5 and low TIMP-3 mRNA levels had a highly significantly shorter DFS in comparison to those patients with low uPAR-del4/5 and high TIMP-3 mRNA expression (P<0.0001). These patients had a more than 6-fold higher risk for disease recurrence or death in multivariate analysis. Therefore, considering the prognostic impact of two proteolytic factors stemming from complementary protease systems may improve the prediction of disease recurrence in breast cancer.
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RECK and TIMP3 are key inhibitors of several MMPs, and their expression is prognostic in a number of common cancers.
“RECK, a membrane-anchored regulator, and TIMP3, the ECM-bound protease regulator, are key inhibitors of several MMPs, and their expression is prognostic in a number of common cancers (28, 53).”
From MicroRNA 21 Promotes Glioma Invasion by Targeting Matrix Metalloproteinase Regulators (2008) · cites this paper as [28]
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- Authors
- Kotzsch, M., Farthmann, J., Meye, A., Fuessel, S., Baretton, G., Tjan-Heijnen, V. C. G., Schmitt, M., Luther, T., Sweep, F. C. G. J., Magdolen, V., & Span, P. N.
- Affiliations
- Technische Universität Dresden (DE)
- Technical University of Munich (DE)
- Radboud University Medical Center (NL)
- ORCID
- Venue
- European Journal of Cancer
- Publisher
- Elsevier BV
- Published
- 2005-11
- Volume
- 41
- Issue
- 17
- Pages
- 2760-2768
- ISSN
- 0959-8049 (ISSN-L)
- OpenAlex
- W2112759379
- Cited by
- 50
- References
- 38
- Citations by year
- 2026: 1 · 2024: 4 · 2023: 1 · 2021: 1 · 2018: 3 · 2017: 1 · 2015: 1 · 2014: 2 · 2013: 1 · 2012: 6
- FWCI
- 1.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Cancer (publishedVersion)
- PubMed (publishedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Deutsche Krebshilfe
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- breast cancer, TIMP-3, mRNA expression, prognostic factors, disease-free survival, recurrence
- MeSH terms
- Adult, Aged, Aged, 80 and over, Breast Neoplasms, Female, Humans, Lymphatic Metastasis, Mastectomy, Middle Aged, Prognosis, Receptors, Cell Surface, RNA, Messenger, Polymerase Chain Reaction, DNA, Complementary, Disease-Free Survival, Tissue Inhibitor of Metalloproteinase-3, Receptors, Urokinase Plasminogen Activator
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