Using the epigenetic field defect to detect prostate cancer in biopsy negative patients

Matthew Truong, Bing Yang, Andrew Livermore, Jennifer Wagner, Puspha Weeratunga, Wei Huang, Rajiv Dhir, Joel Nelson, Daniel W. Lin, David F. Jarrard

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2335-2341
Number of pages7
JournalJournal of Urology
Volume189
Issue number6
DOIs
StatePublished - Jun 1 2013

    Fingerprint

Keywords

  • biopsy
  • diagnosis
  • epigenomics
  • prostate
  • prostatic neoplasms

ASJC Scopus subject areas

  • Urology

Cite this

Truong, M., Yang, B., Livermore, A., Wagner, J., Weeratunga, P., Huang, W., Dhir, R., Nelson, J., Lin, D. W., & Jarrard, D. F. (2013). Using the epigenetic field defect to detect prostate cancer in biopsy negative patients. Journal of Urology, 189(6), 2335-2341. https://doi.org/10.1016/j.juro.2012.11.074