TY  - JOUR
A1  - Litovkin, Kirill
A1  - Van Eynde, Aleyde
A1  - Joniau, Steven
A1  - Lerut, Evelyne
A1  - Laenen, Annouschka
A1  - Gevaert, Thomas
A1  - Gevaert, Olivier
A1  - Spahn, Martin
A1  - Kneitz, Burkhard
A1  - Gramme, Pierre
A1  - Helleputte, Thibault
A1  - Isebaert, Sofie
A1  - Haustermans, Karin
A1  - Bollen, Mathieu
T1  - DNA Methylation-Guided Prediction of Clinical Failure in High-Risk Prostate Cancer
JF  - PLoS ONE
N2  - Background 
Prostate cancer (PCa) is a very heterogeneous disease with respect to clinical outcome. This study explored differential DNA methylation in a priori selected genes to diagnose PCa and predict clinical failure (CF) in high-risk patients. 

Methods 
A quantitative multiplex, methylation-specific PCR assay was developed to assess promoter methylation of the APC, CCND2, GSTP1, PTGS2 and RARB genes in formalin-fixed, paraffin-embedded tissue samples from 42 patients with benign prostatic hyperplasia and radical prostatectomy specimens of patients with high-risk PCa, encompassing training and validation cohorts of 147 and 71 patients, respectively. Log-rank tests, univariate and multivariate Cox models were used to investigate the prognostic value of the DNA methylation. 

Results 
Hypermethylation of APC, CCND2, GSTP1, PTGS2 and RARB was highly cancer-specific. However, only GSTP1 methylation was significantly associated with CF in both independent high-risk PCa cohorts. Importantly, trichotomization into low, moderate and high GSTP1 methylation level subgroups was highly predictive for CF. Patients with either a low or high GSTP1 methylation level, as compared to the moderate methylation groups, were at a higher risk for CF in both the training (Hazard ratio [HR], 3.65; 95% CI, 1.65 to 8.07) and validation sets (HR, 4.27; 95% CI, 1.03 to 17.72) as well as in the combined cohort ( HR, 2.74; 95% CI, 1.42 to 5.27) in multivariate analysis. 

Conclusions 
Classification of primary high-risk tumors into three subtypes based on DNA methylation can be combined with clinico-pathological parameters for a more informative risk-stratification of these PCa patients.
KW  - CpG island hypermethylation
KW  - radical prostatectomy
KW  - promoter methylation
KW  - receptor beta
KW  - gene
KW  - GSTP1
KW  - biomarkers
KW  - diagnosis
KW  - recurrence
KW  - reveals
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151705
VL  - 10
IS  - 6
ER  - 
TY  - JOUR
A1  - Kneitz, Burkhard
A1  - Kalogirou, Charis
A1  - Spahn, Martin
A1  - Krebs, Markus
A1  - Joniau, Steven
A1  - Lerut, Evelyne
A1  - Burger, Maximilian
A1  - Scholz, Claus-Jürgen
A1  - Kneitz, Susanne
A1  - Riedmiller, Hubertus
T1  - MiR-205 Is Progressively Down-Regulated in Lymph Node Metastasis but Fails as a Prognostic Biomarker in High-Risk Prostate Cancer
JF  - International Journal of Molecular Sciences
N2  - 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.
KW  - high-risk prostate cancer
KW  - microRNA
KW  - miR-205
KW  - prognosis
KW  - biomarker
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-97321
ER  -