A four-group urine risk classifier for predicting outcome in prostate cancer patients

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-RN...

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Autores: 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
Formato: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2019
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/167964
Acesso em linha:https://hdl.handle.net/2445/167964
Access Level:acceso abierto
Palavra-chave:Indicadors biològics
Biòpsia
Càncer de pròstata
Orina
Indicators (Biology)
Biopsy
Prostate cancer
Urine
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spelling A four-group urine risk classifier for predicting outcome in prostate cancer patientsConnell, Shea P.Hanna, MarcelMcCarthy, FrankHurst, RachelWebb, MartynCurley, HelenWalker, HelenMills, RobertBall, Richard Y.Sanda, Martin G.Pellegrini, Kathryn L.Patil, DattatrayaPerry, Antoinette S.Schalken, Jack A.Pandha, HardevWhitaker, Hayley C.Dennis, NeningStuttle, ChristineMills, Ian G.Guldvik, IngridMovember GAP1 Urine Biomarker ConsortiumParker, ChrisBrewer, DanielCooper, ColinClark, JeremyIndicadors biològicsBiòpsiaCàncer de pròstataOrinaIndicators (Biology)BiopsyProstate cancerUrineObjectives: 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.Wiley2020202020192020info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersion12 p.application/pdfhttps://hdl.handle.net/2445/167964Articles publicats en revistes (Patologia i Terapèutica Experimental)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésVersió postprint del document publicat a: https://doi.org/10.1111/bju.14811BJU International, 2019, vol. 124, num. 4, p. 609-620https://doi.org/10.1111/bju.14811(c) BJU International, 2019info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1679642026-05-29T05:05:01Z
dc.title.none.fl_str_mv A four-group urine risk classifier for predicting outcome in prostate cancer patients
title A four-group urine risk classifier for predicting outcome in prostate cancer patients
spellingShingle A four-group urine risk classifier for predicting outcome in prostate cancer patients
Connell, Shea P.
Indicadors biològics
Biòpsia
Càncer de pròstata
Orina
Indicators (Biology)
Biopsy
Prostate cancer
Urine
title_short A four-group urine risk classifier for predicting outcome in prostate cancer patients
title_full A four-group urine risk classifier for predicting outcome in prostate cancer patients
title_fullStr A four-group urine risk classifier for predicting outcome in prostate cancer patients
title_full_unstemmed A four-group urine risk classifier for predicting outcome in prostate cancer patients
title_sort A four-group urine risk classifier for predicting outcome in prostate cancer patients
dc.creator.none.fl_str_mv 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
author Connell, Shea P.
author_facet 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
author_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Indicadors biològics
Biòpsia
Càncer de pròstata
Orina
Indicators (Biology)
Biopsy
Prostate cancer
Urine
topic Indicadors biològics
Biòpsia
Càncer de pròstata
Orina
Indicators (Biology)
Biopsy
Prostate cancer
Urine
description 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.
publishDate 2019
dc.date.none.fl_str_mv 2019
2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/167964
url https://hdl.handle.net/2445/167964
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1111/bju.14811
BJU International, 2019, vol. 124, num. 4, p. 609-620
https://doi.org/10.1111/bju.14811
dc.rights.none.fl_str_mv (c) BJU International, 2019
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) BJU International, 2019
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 12 p.
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv Articles publicats en revistes (Patologia i Terapèutica Experimental)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869405431697244160
score 15,81155

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