Please use this identifier to cite or link to this item:
Title: A four-group urine risk classifier for predicting outcome in prostate cancer patients
Author: Connell, Shea P.
Hanna, Marcel
McCarthy, Frank
Hurst, Rachel
Webb, Martyn
Curley, Helen
Walker, Helen
Mills, Robert
Ball, Richard Y.
Sanda, Martin G.
Pellegrini, Kathryn L.
Patil, Dattatraya
Perry, Antoinette S.
Schalken, Jack A.
Pandha, Hardev
Whitaker, Hayley C.
Dennis, Nening
Stuttle, Christine
Mills, Ian G.
Guldvik, Ingrid
Movember GAP1 Urine Biomarker Consortium
Parker, Chris
Brewer, Daniel
Cooper, Colin
Clark, Jeremy
Keywords: Indicadors biològics
Càncer de pròstata
Indicators (Biology)
Prostate cancer
Issue Date: 20-May-2019
Publisher: Wiley
Abstract: Objectives: to develop a risk classifier using urine-derived extracellular vesicle RNA (UEV-RNA) capable of providing diagnostic information of disease status prior to biopsy, and prognostic information for men on active surveillance (AS). Patients and methods: post-digital rectal examination UEV-RNA expression profiles from urine (n = 535, multiple centres) were interrogated with a curated NanoString panel. A LASSO-based Continuation-Ratio model was built to generate four Prostate-Urine-Risk (PUR) signatures for predicting the probability of normal tissue (PUR-1), D'Amico Low-risk (PUR-2), Intermediate-risk (PUR-3), and High-risk (PUR-4) PCa. This model was applied to a test cohort (n = 177) for diagnostic evaluation, and to an AS sub-cohort (n = 87) for prognostic evaluation. Results: each PUR signature was significantly associated with its corresponding clinical category (p<0.001). PUR-4 status predicted the presence of clinically significant Intermediate or High-risk disease, AUC = 0.77 (95% CI: 0.70-0.84). Application of PUR provided a net benefit over current clinical practice. In an AS sub-cohort (n=87), groups defined by PUR status and proportion of PUR-4 had a significant association with time to progression (p<0.001; IQR HR = 2.86, 95% CI:1.83-4.47). PUR-4, when utilised continuously, dichotomised patient groups with differential progression rates of 10% and 60% five years post-urine collection (p<0.001, HR = 8.23, 95% CI:3.26-20.81). Conclusion: UEV-RNA can provide diagnostic information of aggressive PCa prior to biopsy, and prognostic information for men on AS. PUR represents a new & versatile biomarker that could result in substantial alterations to current treatment of PCa patients. This article is protected by copyright. All rights reserved.
Note: Versió postprint del document publicat a:
It is part of: BJU International, 2019, vol. 124, num. 4, p. 609-620
Related resource:
ISSN: 1464-4096
Appears in Collections:Articles publicats en revistes (Patologia i Terapèutica Experimental)

Files in This Item:
File Description SizeFormat 
698883.pdf950.67 kBAdobe PDFView/Open

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.