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dc.contributor.authorConnell, SP
dc.contributor.authorHanna, M
dc.contributor.authorMcCarthy, F
dc.contributor.authorHurst, R
dc.contributor.authorWebb, M
dc.contributor.authorCurley, H
dc.contributor.authorWalker, H
dc.contributor.authorMills, R
dc.contributor.authorBall, RY
dc.contributor.authorSanda, MG
dc.contributor.authorPellegrini, KL
dc.contributor.authorPatil, D
dc.contributor.authorPerry, AS
dc.contributor.authorSchalken, J
dc.contributor.authorPandha, H
dc.contributor.authorWhitaker, H
dc.contributor.authorDennis, N
dc.contributor.authorStuttle, C
dc.contributor.authorMills, IG
dc.contributor.authorGuldvik, I
dc.contributor.authorMovember GAP1 Urine Biomarker Consortium
dc.contributor.authorParker, C
dc.contributor.authorBrewer, DS
dc.contributor.authorCooper, CS
dc.contributor.authorClark, J
dc.date.accessioned2019-08-08T14:36:51Z
dc.date.issued2019-05-20
dc.identifier.citationBJU international, 2019
dc.identifier.issn1464-4096
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3318
dc.identifier.eissn1464-410X
dc.identifier.doi10.1111/bju.14811
dc.description.abstractObjectives 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.formatPrint-Electronic
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectMovember GAP1 Urine Biomarker Consortium
dc.titleA Four-Group Urine Risk Classifier for Predicting Outcome in Prostate Cancer Patients.
dc.typeJournal Article
rioxxterms.versionofrecord10.1111/bju.14811
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
rioxxterms.licenseref.startdate2019-05-20
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfBJU international
pubs.notesNot 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-statusPublished
pubs.embargo.termsNot known
dc.contributor.icrauthorParker, Chrisen


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