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MiR-205 Is Progressively Down-Regulated in Lymph Node Metastasis but Fails as a Prognostic Biomarker in High-Risk Prostate Cancer
Department of Urology and Paediatric Urology, University Hospital Würzburg, Oberdürrbacher Str. 6, Würzburg 97080, Germany
Department of Urology, University Hospital Bern, Holligen, Bern 3010, Switzerland
Department of Urology, University Hospitals Leuven, Herestraat 49, Leuven 3000, Belgium
Department of Pathology, University Hospitals Leuven, Herestraat 49, Leuven 3000, Belgium
Microarray Core Unit, Interdisciplinary Center for Clinical Science, University of Würzburg, Versbacher Straße, Würzburg 97080, Germany
Department of Physiological Chemistry, University of Würzburg, Am Hubland, Würzburg 97074, Germany
* Authors to whom correspondence should be addressed.
Received: 22 July 2013; in revised form: 1 October 2013 / Accepted: 9 October 2013 / Published: 29 October 2013
Abstract: The treatment of high-risk prostate cancer (HRPCa) is a tremendous challenge for uro-oncologists. The identification of predictive moleculobiological markers allowing risk assessment of lymph node metastasis and systemic progression is essential in establishing effective treatment. In the current study, we investigate the prognostic potential of miR-205 in HRPCa study and validation cohorts, setting defined clinical endpoints for both. We demonstrate miR-205 to be significantly down-regulated in over 70% of the HRPCa samples analysed and that reconstitution of miR-205 causes inhibition of proliferation and invasiveness in prostate cancer (PCa) cell lines. Additionally, miR-205 is increasingly down-regulated in lymph node metastases compared to the primary tumour indicating that miR-205 plays a role in migration of PCa cells from the original location into extraprostatic tissue. Nevertheless, down-regulation of miR-205 in primary PCa was not correlated to the synchronous presence of metastasis and failed to predict the outcome for HRPCa patients. Moreover, we found a tendency for miR-205 up-regulation to correlate with an adverse outcome of PCa patients suggesting a pivotal role of miR-205 in tumourigenesis. Overall, we showed that miR-205 is involved in the development and metastasis of PCa, but failed to work as a useful clinical biomarker in HRPCa. These findings might have implications for the use of miR-205 as a prognostic or therapeutic target in HRPCa.
Keywords: high-risk prostate cancer; microRNA; miR-205; prognosis; biomarker
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Kalogirou, C.; Spahn, M.; Krebs, M.; Joniau, S.; Lerut, E.; Burger, M.; Scholz, C.-J.; Kneitz, S.; Riedmiller, H.; Kneitz, B. MiR-205 Is Progressively Down-Regulated in Lymph Node Metastasis but Fails as a Prognostic Biomarker in High-Risk Prostate Cancer. Int. J. Mol. Sci. 2013, 14, 21414-21434.
Kalogirou C, Spahn M, Krebs M, Joniau S, Lerut E, Burger M, Scholz C-J, Kneitz S, Riedmiller H, Kneitz B. MiR-205 Is Progressively Down-Regulated in Lymph Node Metastasis but Fails as a Prognostic Biomarker in High-Risk Prostate Cancer. International Journal of Molecular Sciences. 2013; 14(11):21414-21434.
Kalogirou, Charis; Spahn, Martin; Krebs, Markus; Joniau, Steven; Lerut, Evelyne; Burger, Maximilian; Scholz, Claus-Jürgen; Kneitz, Susanne; Riedmiller, Hubertus; Kneitz, Burkhard. 2013. "MiR-205 Is Progressively Down-Regulated in Lymph Node Metastasis but Fails as a Prognostic Biomarker in High-Risk Prostate Cancer." Int. J. Mol. Sci. 14, no. 11: 21414-21434.