A urine-based DNA methylation assay, ProCUrE, to identify clinically significant prostate cancer.

Autor: Zhao F; Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada.; Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Canada., Olkhov-Mitsel E; Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada.; Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Canada., Kamdar S; Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada.; Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Canada., Jeyapala R; Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada., Garcia J; Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada., Hurst R; Schools of Medicine and Biological Sciences, University of East Anglia, Norwich, Norfolk, UK., Hanna MY; Norfolk and Norwich University Hospital, Norwich, Norfolk, UK., Mills R; Schools of Medicine and Biological Sciences, University of East Anglia, Norwich, Norfolk, UK., Tuzova AV; Cancer Biology and Therapeutics Laboratory, School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Dublin 4, Ireland., O'Reilly E; Cancer Biology and Therapeutics Laboratory, School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Dublin 4, Ireland., Kelly S; Cancer Biology and Therapeutics Laboratory, School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Dublin 4, Ireland., Cooper C; Schools of Medicine and Biological Sciences, University of East Anglia, Norwich, Norfolk, UK., Brewer D; Schools of Medicine and Biological Sciences, University of East Anglia, Norwich, Norfolk, UK.; The Earlham Institute, Norwich, Norfolk, UK., Perry AS; Cancer Biology and Therapeutics Laboratory, School of Biomolecular and Biomedical Science, Conway Institute, University College Dublin, Dublin 4, Ireland., Clark J; Schools of Medicine and Biological Sciences, University of East Anglia, Norwich, Norfolk, UK., Fleshner N; Division of Urology, University Health Network, University of Toronto, Toronto, Canada., Bapat B; Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada. bapat@lunenfeld.ca.; Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Canada. bapat@lunenfeld.ca.; Division of Urology, University Health Network, University of Toronto, Toronto, Canada. bapat@lunenfeld.ca.
Jazyk: angličtina
Zdroj: Clinical epigenetics [Clin Epigenetics] 2018 Nov 23; Vol. 10 (1), pp. 147. Date of Electronic Publication: 2018 Nov 23.
DOI: 10.1186/s13148-018-0575-z
Abstrakt: 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.
Databáze: MEDLINE
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