| Employing the Epigenetic Field Defect to Detect Prostate Cancer in Biopsy-Negative Patients. | |
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MedLine Citation:
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PMID: 23159584 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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PURPOSE: To determine whether a novelcombination of fielddefect DNA methylation markers can predict the presence of PCa using histologically normal transrectal ultrasound-guided biopsy cores. MATERIALS AND METHODS: Methylation was assessed using quantitative pyrosequencing in a training set consisting of 65 non-tumor associated (NTA) and tumor associated (TA) prostate tissues from the University of Wisconsin. Amultiplex model was generated using multivariate logistic regression and externally validated in a blinded fashion using a set of 47 NTA and TA biopsy specimens from the University of Washington. RESULTS: Robust methylation differences were observed for all genes at all CpGs assayed (p<0.0001). Regression models incorporating individual genes (EVX1, CAV1, and FGF1) and a gene combination (EVX1 and FGF1) discriminated between NTA and TA tissues in the original training set (AUC 0.796-0.898, p<0.001). Upon external validation, uniplex models incorporating EVX1, CAV1, or FGF1 discriminated between TA and NTA biopsy-negative specimens with an AUC of 0.702, 0.696, and 0.658, respectively (p<0.05). Furthermore, amultiplex model (EVX1 and FGF1) identified PCa patients with an AUC of 0.774 (p=0.001) and had a negative predictive value of 0.909.Comparison between 2 separate cores within patients in this validation set revealed similar methylation defects indicating a widespread field defect was being detected. CONCLUSIONS: A widespread epigenetic fielddefect can be utilized to detect the existence of PCa in patients with histologically negative biopsies. This assay is unique in that it detects alterations in non-tumor cells. With further validation, this markercombination (EVX1 and FGF1) has the potential to decrease the need for repeated prostate biopsies, a procedure associated with cost and complications. |
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Authors:
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Matthew Truong; Bing Yang; Andrew Livermore; Jennifer Wagner; Puspha Weeratunga; Wei Huang; Rajiv Dhir; Joel Nelson; Daniel W Lin; David F Jarrard |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-11-15 |
Journal Detail:
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Title: The Journal of urology Volume: - ISSN: 1527-3792 ISO Abbreviation: J. Urol. Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-11-19 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0376374 Medline TA: J Urol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved. |
Affiliation:
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University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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