TY  - JOUR
A1  - Schubert, Maria
A1  - Joniau, Steven
A1  - Gontero, Paolo
A1  - Kneitz, Susanne
A1  - Scholz, Claus-Jürgen
A1  - Kneitz, Burkhard
A1  - Briganti, Alberto
A1  - Karnes, R. Jeffery
A1  - Tombal, Bertrand
A1  - Walz, Jochen
A1  - Hsu, Chao-Yu
A1  - Marchioro, Giansilvio
A1  - Bader, Pia
A1  - Bangma, Chris
A1  - Frohneberg, Detlef
A1  - Graefen, Markus
A1  - Schröder, Fritz
A1  - van Cangh, Paul
A1  - van Poppel, Hein
A1  - Spahn, Martin
T1  - The Role of Adjuvant Hormonal Treatment after Surgery for Localized High-Risk Prostate Cancer: Results of a Matched Multiinstitutional Analysis
JF  - Advances in Urology
N2  - Introduction. To assess the role of adjuvant androgen deprivation therapy (ADT) in high-risk prostate cancer patients (PCa) after surgery. Materials and Methods. The analysis case matched 172 high-risk PCa patients with positive section margins or non-organ confined disease and negative lymph nodes to receive adjuvant ADT (group 1, n=86 ) or no adjuvant ADT (group 2, n=86). Results. Only 11.6% of the patients died, 2.3% PCa related. Estimated 5–10-year clinical progression-free survival was 96.9% (94.3%) for group 1 and 73.7% (67.0%) for group 2, respectively. Subgroup analysis identified men with T2/T3a tumors at low-risk and T3b margins positive disease at higher risk for progression. Conclusion. Patients with T2/T3a tumors are at low-risk for metastatic disease and cancer-related death and do not need adjuvant ADT. We identified men with T3b margin positive disease at highest risk for clinical progression. These patients benefit from immediate adjuvant ADT.
KW  - prostate cancer
KW  - adjuvant hormonal treatment
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-137712
VL  - 2012
ER  - 
TY  - JOUR
A1  - Schubert, Maria
A1  - Spahn, Martin
A1  - Kneitz, Susanne
A1  - Scholz, Claus Jürgen
A1  - Joniau, Steven
A1  - Stroebel, Philipp
A1  - Riedmiller, Hubertus
A1  - Kneitz, Burkhard
T1  - 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
JF  - PLoS ONE
N2  - 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.
KW  - biomarkers
KW  - gene expression
KW  - gene targeting
KW  - luciferase
KW  - MircoRNA
KW  - microarrays
KW  - oncogenes
KW  - prostate cancer
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96825
ER  -