Document Detail


Using the epigenetic field defect to detect prostate cancer in biopsy negative patients.
MedLine Citation:
PMID:  23159584     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: We determined whether a novel combination of field defect DNA methylation markers could predict the presence of prostate cancer using histologically normal transrectal ultrasound guided biopsy cores.
MATERIALS AND METHODS: Methylation was assessed using quantitative Pyrosequencing® in a training set consisting of 65 nontumor and tumor associated prostate tissues from University of Wisconsin. A multiplex model was generated using multivariate logistic regression and externally validated in blinded fashion in a set of 47 nontumor and tumor associated biopsy specimens from University of Washington.
RESULTS: We observed robust methylation differences in 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 nontumor from tumor associated tissues in the original training set (AUC 0.796-0.898, p <0.001). On external validation uniplex models incorporating EVX1, CAV1 or FGF1 discriminated tumor from nontumor associated biopsy negative specimens (AUC 0.702, 0.696 and 0.658, respectively, p <0.05). A multiplex model (EVX1 and FGF1) identified patients with prostate cancer (AUC 0.774, p = 0.001) and had a negative predictive value of 0.909. Comparison between 2 separate cores in patients in this validation set revealed similar methylation defects, indicating detection of a widespread field defect.
CONCLUSIONS: A widespread epigenetic field defect can be used to detect prostate cancer in patients with histologically negative biopsies. To our knowledge this assay is unique, in that it detects alterations in nontumor cells. With further validation this marker combination (EVX1 and FGF1) has the potential to decrease the need for repeat prostate biopsies, a procedure associated with cost and complications.
Authors:
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:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-11-15
Journal Detail:
Title:  The Journal of urology     Volume:  189     ISSN:  1527-3792     ISO Abbreviation:  J. Urol.     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-05-13     Completed Date:  2013-07-17     Revised Date:  2014-03-20    
Medline Journal Info:
Nlm Unique ID:  0376374     Medline TA:  J Urol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2335-41     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Aged
Aged, 80 and over
Biopsy, Needle
DNA Methylation*
Epigenomics / methods*
Fibroblast Growth Factor 1 / genetics*,  metabolism
Gene Expression Regulation, Neoplastic
Genetic Markers
Homeodomain Proteins / genetics*,  metabolism
Humans
Immunohistochemistry
Male
Middle Aged
Predictive Value of Tests
Prostatic Neoplasms / genetics*,  pathology*
Reference Values
Regression Analysis
Reproducibility of Results
Risk Factors
Sensitivity and Specificity
Statistics, Nonparametric
Tissue Culture Techniques
Grant Support
ID/Acronym/Agency:
5R01CA 131255/CA/NCI NIH HHS; 5R01CA097131/CA/NCI NIH HHS; KL2 RR02012/RR/NCRR NIH HHS; KL2 RR025012/RR/NCRR NIH HHS; P30 CA014520/CA/NCI NIH HHS; R01 CA097131/CA/NCI NIH HHS; R01 CA131255/CA/NCI NIH HHS; UL1 RR025011/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Genetic Markers; 0/Homeodomain Proteins; 104781-85-3/Fibroblast Growth Factor 1; 130173-73-8/EVX1 protein, human
Comments/Corrections
Comment In:
J Urol. 2013 Jun;189(6):2020-1   [PMID:  23465550 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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