9732
2013
eng
article
1
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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
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.
International Journal of Molecular Sciences
10.3390/ijms141121414
urn:nbn:de:bvb:20-opus-97321
Microarray Core Unit, Interdisciplinary Center for Clinical Science, University of Würzburg, Versbacher Straße, Würzburg 97080, Germany
In: International Journal of Molecular Sciences (2013) 14: 11, 21414-34, doi:10.3390/ijms141121414
Burkhard Kneitz
Charis Kalogirou
Martin Spahn
Markus Krebs
Steven Joniau
Evelyne Lerut
Maximilian Burger
Claus-Jürgen Scholz
Susanne Kneitz
Hubertus Riedmiller
eng
uncontrolled
high-risk prostate cancer
eng
uncontrolled
microRNA
eng
uncontrolled
miR-205
eng
uncontrolled
prognosis
eng
uncontrolled
biomarker
Medizin und Gesundheit
open_access
Urologische Klinik und Poliklinik
Theodor-Boveri-Institut für Biowissenschaften
Förderzeitraum 2013
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/9732/Kneitz_ijms141121414.pdf
9682
2013
eng
article
1
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Distinct microRNA Expression Profile in Prostate Cancer Patients with Early Clinical Failure and the Impact of let-7 as Prognostic Marker in High-Risk Prostate Cancer
Background
The identification of additional prognostic markers to improve risk stratification and to avoid overtreatment is one of the most urgent clinical needs in prostate cancer (PCa). MicroRNAs, being important regulators of gene expression, are promising biomarkers in various cancer entities, though the impact as prognostic predictors in PCa is poorly understood. The aim of this study was to identify specific miRNAs as potential prognostic markers in high-risk PCa and to validate their clinical impact.
Methodology and Principal Findings
We performed miRNA-microarray analysis in a high-risk PCa study group selected by their clinical outcome (clinical progression free survival (CPFS) vs. clinical failure (CF)). We identified seven candidate miRNAs (let-7a/b/c, miR-515-3p/5p, -181b, -146b, and -361) that showed differential expression between both groups. Further qRT-PCR analysis revealed down-regulation of members of the let-7 family in the majority of a large, well-characterized high-risk PCa cohort (n = 98). Expression of let-7a/b/and -c was correlated to clinical outcome parameters of this group. While let-7a showed no association or correlation with clinical relevant data, let-7b and let-7c were associated with CF in PCa patients and functioned partially as independent prognostic marker. Validation of the data using an independent high-risk study cohort revealed that let-7b, but not let-7c, has impact as an independent prognostic marker for BCR and CF. Furthermore, we identified HMGA1, a non-histone protein, as a new target of let-7b and found correlation of let-7b down-regulation with HMGA1 over-expression in primary PCa samples.
Conclusion
Our findings define a distinct miRNA expression profile in PCa cases with early CF and identified let-7b as prognostic biomarker in high-risk PCa. This study highlights the importance of let-7b as tumor suppressor miRNA in high-risk PCa and presents a basis to improve individual therapy for high-risk PCa patients.
PLoS ONE
10.1371/journal.pone.0065064
urn:nbn:de:bvb:20-opus-96825
In: PLoS ONE (2013) 8: 6, doi:10.1371/journal.pone.0065064
Maria Schubert
Martin Spahn
Susanne Kneitz
Claus Jürgen Scholz
Steven Joniau
Philipp Stroebel
Hubertus Riedmiller
Burkhard Kneitz
eng
uncontrolled
biomarkers
eng
uncontrolled
gene expression
eng
uncontrolled
gene targeting
eng
uncontrolled
luciferase
eng
uncontrolled
MircoRNA
eng
uncontrolled
microarrays
eng
uncontrolled
oncogenes
eng
uncontrolled
prostate cancer
Medizin und Gesundheit
open_access
Urologische Klinik und Poliklinik
Theodor-Boveri-Institut für Biowissenschaften
Förderzeitraum 2013
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/9682/Schubert_journal.pone.0065064.pdf