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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Detalles Bibliográficos
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
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2019
País:España
Institución: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
Acceso en línea:https://hdl.handle.net/2445/167964
Access Level:acceso abierto
Palabra clave:Indicadors biològics
Biòpsia
Càncer de pròstata
Orina
Indicators (Biology)
Biopsy
Prostate cancer
Urine
Descripción
Sumario: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.

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