Combined DNA-methylation intensity and clinical risk score to stratify patients for high-grade disease
| Autor: | William E. Grizzle, Leander Van Neste, Sandra M. Gaston, George W. Adams, Grant D. Stewart, David J. Harrison, Gary P. Kearney, Jonathan I. Epstein, Alan W. Partin, Wim Van Criekinge |
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| Rok vydání: | 2016 |
| Předmět: | |
| Zdroj: | Journal of Clinical Oncology. 34:51-51 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | 51 Background: Prostate cancer (PCa) diagnostics remains challenging due to fear of over-diagnosis and overtreatment. Due to low accuracy of PSA too many men are biopsied that do not have a subsequent PCa diagnosis or that have indolent disease. Furthermore, persistent risk factors and fear of missed PCa leads to many unnecessary repeat biopsies. Most prostate tumors have epigenetic DNA-methylation aberrations, which display a field effect that can be observed in normal-appearing surrounding tissue, and that could help alleviate biopsy-sampling errors. Methods: A training cohort of methylation-positive men with a negative index biopsy followed by either a Gleason score (GS) ≥ 7 (n=43) or cancer-negative (n=226) repeat biopsy was evaluated. Using the initial negative biopsy, men were stratified for the likelihood of harboring high-grade PCa focusing on a methylation intensity algorithm involving GSTP1, RASSF1 and APC. This algorithm was validated in a cohort of 102 men, with either a PCa-free (n=20), GS6 (n=46), or GS≥7 (n=36) biopsies. Results: The methylation intensity-based algorithm was developed on PCa-negative index biopsies and optimized to predict the presence of GS≥7 cancer in a repeat biopsy. The methylation intensity was significantly higher in GS≥7 compared to PCa-free repeat biopsies (p |
| Databáze: | OpenAIRE |
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