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Title: A urine-based DNA methylation assay, ProCUrE, to identify clinically significant prostate cancer
Author: Zhao, Fang
Olkhov-Mitsel, Ekaterina
Kamdar, Shivani
Jeyapala, Renu
Garcia, Julia
Hurst, Rachel
Hanna, Marcelino Yazbek
Mills, Robert
Tuzova, Alexandra V.
O'Reilly, Eve
Kelly, Sarah
Cooper, Colin
Movember Urine Biomarker Consortium
Brewer, Daniel
Perry, Antoinette S.
Clark, Jeremy
Fleshner, Neil
Bapat, Bharati
Keywords: Càncer de pròstata
Indicadors biològics
Prostate cancer
Indicators (Biology)
Issue Date: 23-Nov-2018
Publisher: BioMed Central
Abstract: Background: prevention of unnecessary biopsies and overtreatment 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) diseases 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 in risk categories ranging 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.
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It is part of: Clinical Epigenetics, 2018, vol. 10, num. 1, p. 147
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ISSN: 1868-7075
Appears in Collections:Articles publicats en revistes (Patologia i Terapèutica Experimental)

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