dc.contributor.author | Connell, SP | |
dc.contributor.author | Hanna, M | |
dc.contributor.author | McCarthy, F | |
dc.contributor.author | Hurst, R | |
dc.contributor.author | Webb, M | |
dc.contributor.author | Curley, H | |
dc.contributor.author | Walker, H | |
dc.contributor.author | Mills, R | |
dc.contributor.author | Ball, RY | |
dc.contributor.author | Sanda, MG | |
dc.contributor.author | Pellegrini, KL | |
dc.contributor.author | Patil, D | |
dc.contributor.author | Perry, AS | |
dc.contributor.author | Schalken, J | |
dc.contributor.author | Pandha, H | |
dc.contributor.author | Whitaker, H | |
dc.contributor.author | Dennis, N | |
dc.contributor.author | Stuttle, C | |
dc.contributor.author | Mills, IG | |
dc.contributor.author | Guldvik, I | |
dc.contributor.author | Movember GAP1 Urine Biomarker Consortium | |
dc.contributor.author | Parker, C | |
dc.contributor.author | Brewer, DS | |
dc.contributor.author | Cooper, CS | |
dc.contributor.author | Clark, J | |
dc.date.accessioned | 2019-08-08T14:36:51Z | |
dc.date.issued | 2019-05-20 | |
dc.identifier.citation | BJU international, 2019 | |
dc.identifier.issn | 1464-4096 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3318 | |
dc.identifier.eissn | 1464-410X | |
dc.identifier.doi | 10.1111/bju.14811 | |
dc.description.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. | |
dc.format | Print-Electronic | |
dc.language | eng | |
dc.language.iso | eng | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Movember GAP1 Urine Biomarker Consortium | |
dc.title | A Four-Group Urine Risk Classifier for Predicting Outcome in Prostate Cancer Patients. | |
dc.type | Journal Article | |
rioxxterms.versionofrecord | 10.1111/bju.14811 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by-nc-nd/4.0 | |
rioxxterms.licenseref.startdate | 2019-05-20 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | BJU international | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.publication-status | Published | |
pubs.embargo.terms | Not known | |
dc.contributor.icrauthor | Parker, Chris | |