Academic Journal
DNA Methylation-Guided Prediction of Clinical Failure in High-Risk Prostate Cancer.
| العنوان: | DNA Methylation-Guided Prediction of Clinical Failure in High-Risk Prostate Cancer. |
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| المؤلفون: | 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 |
| المصدر: | PLoS ONE, Vol 10, Iss 6, p e0130651 (2015) |
| بيانات النشر: | Public Library of Science (PLoS), 2015. |
| سنة النشر: | 2015 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | Medicine, Science |
| الوصف: | BackgroundProstate 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.MethodsA 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.ResultsHypermethylation 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.ConclusionsClassification 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1932-6203 |
| Relation: | https://doaj.org/toc/1932-6203 |
| DOI: | 10.1371/journal.pone.0130651 |
| URL الوصول: | https://doaj.org/article/32869977bdee4077b96941b4ea59216a |
| رقم الانضمام: | edsdoj.32869977bdee4077b96941b4ea59216a |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 19326203 |
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| DOI: | 10.1371/journal.pone.0130651 |