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|Title:||A four-group urine risk classifier for predicting outcome in prostate cancer patients|
|Author:||Connell, Shea P.|
Ball, Richard Y.
Sanda, Martin G.
Pellegrini, Kathryn L.
Perry, Antoinette S.
Schalken, Jack A.
Whitaker, Hayley C.
Mills, Ian G.
Movember GAP1 Urine Biomarker Consortium
Càncer de pròstata
|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: https://doi.org/10.1111/bju.14811|
|It is part of:||BJU International, 2019, vol. 124, num. 4, p. 609-620|
|Appears in Collections:||Articles publicats en revistes (Patologia i Terapèutica Experimental)|
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