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...
| Authors: | ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; |
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| Format: | Article |
| Status: | Accepted version |
| Publication date: | 2019 |
| Country: | España |
| Institution: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repository: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:2445/167964 |
| Online Access: | https://hdl.handle.net/2445/167964 |
| Access Level: | Open access |
| Keyword: | Indicadors biològics Biòpsia Càncer de pròstata Orina Indicators (Biology) Biopsy Prostate cancer Urine |
| _version_ | 1878731396640407552 |
|---|---|
| author | Connell, Shea P. |
| 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 |
| author_browse | Ball, Richard Y. Brewer, Daniel Clark, Jeremy Connell, Shea P. Cooper, Colin Curley, Helen Dennis, Nening Guldvik, Ingrid Hanna, Marcel Hurst, Rachel McCarthy, Frank Mills, Ian G. Mills, Robert Movember GAP1 Urine Biomarker Consortium Pandha, Hardev Parker, Chris Patil, Dattatraya Pellegrini, Kathryn L. Perry, Antoinette S. Sanda, Martin G. Schalken, Jack A. Stuttle, Christine Walker, Helen Webb, Martyn Whitaker, Hayley C. |
| 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 |
| collection | Recercat. Dipósit de la Recerca de Catalunya |
| 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_2ec00ad3be8ec24cf137d40a2d3c37ae |
| institution | 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) |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:recercat.cat:2445/167964 |
| publishDate | 2019 |
| publishDateSort | 2019 |
| publisher | Wiley |
| publisherStr | Wiley |
| reponame_str | Recercat. Dipósit de la Recerca de Catalunya |
| spelling | A four-group urine risk classifier for predicting outcome in prostate cancer patients 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 Indicadors biològics Biòpsia Càncer de pròstata Orina Indicators (Biology) Biopsy Prostate cancer Urine 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. Wiley https://hdl.handle.net/2445/167964 |
| 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 |
| status_str | acceptedVersion |
| title | 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_short | 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 |
| topic | Indicadors biològics Biòpsia Càncer de pròstata Orina Indicators (Biology) Biopsy Prostate cancer Urine |
| topic_facet | Indicadors biològics Biòpsia Càncer de pròstata Orina Indicators (Biology) Biopsy Prostate cancer Urine |
| url | https://hdl.handle.net/2445/167964 |