A urine based DNA methylation Assay, ProCUrE, to identify clinically significant prostate cancer

Zhao, Fang, Olkhov-Mitsel, Ekaterina, Kamdar, Shivani, Jeyapala, Renu, Garcia, Julia, Hurst, Rachel, Yazbek Hanna, Marcelino, Mills, Robert, Tuzova, Alexandra, O'Reilly, Eve, Kelly, Sarah, Cooper, Colin, Brewer, Daniel, Perry, Antoinette, Clark, Jeremy, Fleshner, Neil and Bapat, Bharati (2018) A urine based DNA methylation Assay, ProCUrE, to identify clinically significant prostate cancer. Clinical Epigenetics, 10. ISSN 1868-7075

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Abstract

Background: Prevention of unnecessary biopsies and over-treatment of indolent disease remains a challenge in the management of prostate cancer. Novel non-invasive tests that can identify clinically significant (intermediate-risk and high-risk) disease are needed to improve risk stratification and monitoring of prostate cancer patients. Here, we investigated a panel of six DNA methylation biomarkers in urine samples collected post-digital rectal exam from patients undergoing prostate biopsy, for their utility to guide decision making for diagnostic biopsy and early detection of aggressive prostate cancer.  Results: We recruited 408 patients ranging in risk categories from benign to low-, intermediate- and high-risk prostate cancer from three international cohorts. Patients were separated into 2/3 training and 1/3 validation cohorts. Methylation biomarkers were analyzed in post-digital rectal exam urinary sediment DNA by quantitative MethyLight assay and investigated for their association with any or aggressive prostate cancers. We developed a Prostate Cancer Urinary Epigenetic (ProCUrE) assay based on an optimal two-gene (HOXD3 and GSTP1) LASSO model, derived from methylation values in the training cohort and assessed ProCUrE’s diagnostic and prognostic ability for prostate cancer in both the training and validation cohorts. ProCUrE demonstrated improved prostate cancer diagnosis and identification of patients with clinically significant disease in both the training and validation cohorts. Using three different risk stratification criteria (Gleason score, D’Amico criteria, and CAPRA score) we found that the positive predictive value for ProCUrE was higher (59.4%-78%) than prostate specific antigen (PSA) (38.2%-72.1%) for all risk category comparisons. ProCUrE also demonstrated additive value to PSA in identifying GS≥7 PCa compared to PSA alone (DeLong’s test p=0.039), as well as additive value to the PCPT risk calculator for identifying any PCa and GS≥7 PCa (DeLong’s test p=0.011 and 0.022 respectively).  Conclusions: ProCUrE is a promising non-invasive urinary methylation assay for the early detection and prognostication of prostate cancer. ProCUrE has the potential to supplement PSA testing to identify patients with clinically significant prostate cancer.

Item Type: Article
Uncontrolled Keywords: prostate cancer,psa,urine,dna methylation,biomarker,early detection,overtreatment
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: LivePure Connector
Date Deposited: 19 Nov 2018 14:31
Last Modified: 20 Aug 2020 23:52
URI: https://ueaeprints.uea.ac.uk/id/eprint/68948
DOI: 10.1186/s13148-018-0575-z

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