epiCaPture: a urine DNA methylation test for early detection of aggressive prostate cancer

O'Reilly, Eve, Tuzova, Alexandra, Walsh, Anna, Russell, Niamh, O’Brien, Odharnaith, Kelly, Sarah, Dhomhnallain, Odharna, DeBarra, Liam, Dale, Connie, Brugman, Rick, Clarke, Gavin, Schmidt, Olivia, O'Meachair, Shane, Patil, Dattatraya, Pellegrini, Kathryn, Fleshner, Neil, Garcia, Julia, Zhao, Fang, Finn, Stephen, Mills, Robert, Y. Hanna, Marcelino, Hurst, Rachel, McEvoy, Elizabeth, Gallagher, William, Manecksha, Rustom, Cooper, Colin, Brewer, Daniel, Bapat, Bharati, Sanda, Martin, Clark, Jeremy and Perry, Antoinette (2019) epiCaPture: a urine DNA methylation test for early detection of aggressive prostate cancer. JCO Precision Oncology. ISSN 2473-4284

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      Abstract

      Purpose: Liquid biopsies that non-invasively detect molecular correlates of aggressive prostate cancer (PCa) could be employed to triage patients; reducing the burdens of unnecessary invasive prostate biopsy, and enabling early detection of high-risk disease. DNA hypermethylation is amongst the earliest and most frequent aberrations in PCa. We investigated the accuracy of a 6 gene DNA methylation panel (epiCaPture) at detecting PCa, high-grade (Gleason score ≥8) and high-risk (D’Amico and CAPRA) PCa from urine. Patients and Methods: Prognostic utility of epiCaPture genes was first validated in two independent prostate tissue cohorts. epiCaPture was assessed in a multicentre prospective study of 463 men undergoing prostate biopsy. epiCaPture was performed by quantitative methylation specific PCR in DNA isolated from pre-biopsy urine sediments, and evaluated by ROC and decision curves (clinical benefit). The epiCaPture score was developed and validated on a 2/3: 1/3 training: test set. Results: Higher methylation of epiCaPture genes was significantly associated with increasing aggressiveness in PCa tissues. In urine, AUCs were 0.64, O.86 and 0.83 for detecting PCa, high-grade PCa and high-risk PCa, respectively. Decision curves revealed a net benefit across relevant threshold probabilities. Independent analysis of two epiCaPture genes in the same clinical cohort provided analytical validation. Parallel epiCaPture analysis in urine and matched biopsy cores showed added value of a liquid biopsy. Conclusion: epiCaPture is a urine DNA methylation test for high-risk PCa. Its tumor- specificity out-performs that of PSA (>3ng/ml). Used as an adjunct to PSA, epiCaPture could aid patient stratification, to determine need for biopsy.

      Item Type: Article
      Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
      Depositing User: LivePure Connector
      Date Deposited: 20 Sep 2018 16:30
      Last Modified: 08 May 2019 00:53
      URI: https://ueaeprints.uea.ac.uk/id/eprint/68317
      DOI: 10.1200/PO.18.00134

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