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DNA Methylation-Guided Prediction of Clinical Failure in High-Risk Prostate Cancer

Please always quote using this URN: urn:nbn:de:bvb:20-opus-151705
  • 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 prostatectomyBackground 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.show moreshow less

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Metadaten
Author: Kirill Litovkin, Aleyde Van Eynde, Steven Joniau, Evelyne Lerut, Annouschka Laenen, Thomas Gevaert, Olivier Gevaert, Martin Spahn, Burkhard Kneitz, Pierre Gramme, Thibault Helleputte, Sofie Isebaert, Karin Haustermans, Mathieu Bollen
URN:urn:nbn:de:bvb:20-opus-151705
Document Type:Journal article
Faculties:Medizinische Fakultät / Urologische Klinik und Poliklinik
Language:English
Parent Title (English):PLoS ONE
Year of Completion:2015
Volume:10
Issue:6
Pagenumber:e0130651
Source:PLoS ONE 10(6): e0130651 (2015). DOI: 10.1371/journal.pone.0130651
DOI:https://doi.org/10.1371/journal.pone.0130651
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:CpG island hypermethylation; GSTP1; biomarkers; diagnosis; gene; promoter methylation; radical prostatectomy; receptor beta; recurrence; reveals
Release Date:2017/10/27
Licence (German):License LogoCC 0: Public Domain Dedication