@article{AlJanabiTaubertLohseFischeretal.2014, author = {Al-Janabi, Omar and Taubert, Helge and Lohse-Fischer, Andrea and Fr{\"o}hner, Michael and Wach, Sven and St{\"o}hr, Robert and Keck, Bastian and Burger, Max and Wieland, Wolf and Erdmann, Kati and Wirth, Manfred P. and Wullich, Bernd and Baretton, Gustavo and Magdolen, Viktor and Kotzsch, Mathias and F{\"u}ssel, Susanne}, title = {Association of Tissue mRNA and Serum Antigen Levels of Members of the Urokinase-Type Plasminogen Activator System with Clinical and Prognostic Parameters in Prostate Cancer}, series = {Biomed Research International}, journal = {Biomed Research International}, number = {972587}, issn = {2314-6141}, doi = {10.1155/2014/972587}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-117967}, year = {2014}, abstract = {The objective was to determine the mRNA expression and protein levels of uPA system components in tissue specimens and serum samples, respectively, from prostate cancer (PCa) patients and to assess their association with clinicopathological parameters and overall survival (OS). The mRNA expression levels of uPA, its receptor (uPAR), and its inhibitor type 1 (PAI-1) were analyzed in corresponding malignant and adjacent nonmalignant tissue specimens from 132 PCa patients by quantitative PCR. Preoperative serum samples from 81 PCa patients were analyzed for antigen levels of uPA system members by ELISA. RNA levels of uPA system components displayed significant correlations with each other in the tumor tissues. A significantly decreased uP AmRNA expression in PCa compared to the corresponding nonmalignant tissue was detected. High uPA mRNA level was significantly associated with a high Gleason score. Elevated concentration of soluble uPAR (suPAR) in serum was significantly associated with a poor OS of PCa patients (P = 0.022). PCa patients with high suPAR levels have a significantly higher risk of death (multivariate Cox's regression analysis; IIR - 7.12, P - 0.027). The association of high suPAR levels with poor survival of PCa patients suggests a prognostic impact of suPAR levels in serum of cancer patients.}, language = {en} } @article{LitovkinVanEyndeJoniauetal.2015, author = {Litovkin, Kirill and Van Eynde, Aleyde and Joniau, Steven and Lerut, Evelyne and Laenen, Annouschka and Gevaert, Thomas and Gevaert, Olivier and Spahn, Martin and Kneitz, Burkhard and Gramme, Pierre and Helleputte, Thibault and Isebaert, Sofie and Haustermans, Karin and Bollen, Mathieu}, title = {DNA Methylation-Guided Prediction of Clinical Failure in High-Risk Prostate Cancer}, series = {PLoS ONE}, volume = {10}, journal = {PLoS ONE}, number = {6}, doi = {10.1371/journal.pone.0130651}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151705}, pages = {e0130651}, year = {2015}, abstract = {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.}, language = {en} }