Clinical validation of a biopsy‐based six‐gene signature prognostic for aggressive prostate cancer

Abstract Objectives This study aimed to clinically validate the six‐gene prognostic molecular clinical risk score (MCRS) for the prediction of aggressive prostate cancer in diagnostic biopsy tissue. Methods MCRS was evaluated in prostate biopsy tissue from a Swedish cohort of men with prostate cance...

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Main Authors: Agnieszka Krzyzanowska, Debra F. Higgins, Stephen Barron, Tony Loughman, Amanda O'Neill, Katherine M. Sheehan, Chan‐Ju Angel Wang, Bozena Fender, Leah McGuire, Joanna Fay, Anthony O'Grady, Des O'Leary, R. William Watson, Anders Bjartell, William M. Gallagher
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:BJUI Compass
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Online Access:https://doi.org/10.1002/bco2.474
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author Agnieszka Krzyzanowska
Debra F. Higgins
Stephen Barron
Tony Loughman
Amanda O'Neill
Katherine M. Sheehan
Chan‐Ju Angel Wang
Bozena Fender
Leah McGuire
Joanna Fay
Anthony O'Grady
Des O'Leary
R. William Watson
Anders Bjartell
William M. Gallagher
author_facet Agnieszka Krzyzanowska
Debra F. Higgins
Stephen Barron
Tony Loughman
Amanda O'Neill
Katherine M. Sheehan
Chan‐Ju Angel Wang
Bozena Fender
Leah McGuire
Joanna Fay
Anthony O'Grady
Des O'Leary
R. William Watson
Anders Bjartell
William M. Gallagher
author_sort Agnieszka Krzyzanowska
collection DOAJ
description Abstract Objectives This study aimed to clinically validate the six‐gene prognostic molecular clinical risk score (MCRS) for the prediction of aggressive prostate cancer in diagnostic biopsy tissue. Methods MCRS was evaluated in prostate biopsy tissue from a Swedish cohort of men with prostate cancer (UPCA, n = 100). The primary outcome of adverse pathology and secondary outcomes of high primary Gleason (≥G4) and high pathological T‐stage (≥T3) were assessed by likelihood ratio statistics and area under the receiver operating characteristic curves from logistic regression models; time to biochemical recurrence was assessed by likelihood ratio statistics and C‐indexes from Cox proportional hazard regression models. Results Biopsy MCRS was significantly prognostic (p < 0.0001) and added significant prognostic value to clinico‐pathological features for adverse pathology, high primary Gleason and high pathological T‐stage (p < 0.0001). MCRS was prognostic for biochemical recurrence and added some, albeit non‐significant, prognostic value to clinical risk stratifiers, which could reflect the low number of recurrence events in the cohort. Conclusion Biopsy‐based MCRS improves risk stratification over standard clinical and pathological information and optimises patient management after diagnosis of prostate cancer.
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spelling doaj-art-f0067809c9c14348b7a0481287d2ea132025-01-31T00:14:32ZengWileyBJUI Compass2688-45262025-01-0161n/an/a10.1002/bco2.474Clinical validation of a biopsy‐based six‐gene signature prognostic for aggressive prostate cancerAgnieszka Krzyzanowska0Debra F. Higgins1Stephen Barron2Tony Loughman3Amanda O'Neill4Katherine M. Sheehan5Chan‐Ju Angel Wang6Bozena Fender7Leah McGuire8Joanna Fay9Anthony O'Grady10Des O'Leary11R. William Watson12Anders Bjartell13William M. Gallagher14Department of Translational Medicine, Division of Urological Cancers, Faculty of Medicine Lund University Lund SwedenOncoAssure Ltd, NovaUCD Dublin IrelandOncoAssure Ltd, NovaUCD Dublin IrelandOncoAssure Ltd, NovaUCD Dublin IrelandUCD School of Medicine, UCD Conway Institute of Biomolecular and Biomedical Research University College Dublin Dublin IrelandPathology, RCSI Education and Research Centre Beaumont Hospital Dublin IrelandOncoAssure Ltd, NovaUCD Dublin IrelandOncoAssure Ltd, NovaUCD Dublin IrelandOncoAssure Ltd, NovaUCD Dublin IrelandRCSI Biobank, RCSI Education and Research Centre Beaumont Hospital Dublin IrelandPathology, RCSI Education and Research Centre Beaumont Hospital Dublin IrelandOncoAssure Ltd, NovaUCD Dublin IrelandUCD School of Medicine, UCD Conway Institute of Biomolecular and Biomedical Research University College Dublin Dublin IrelandDepartment of Translational Medicine, Division of Urological Cancers, Faculty of Medicine Lund University Lund SwedenOncoAssure Ltd, NovaUCD Dublin IrelandAbstract Objectives This study aimed to clinically validate the six‐gene prognostic molecular clinical risk score (MCRS) for the prediction of aggressive prostate cancer in diagnostic biopsy tissue. Methods MCRS was evaluated in prostate biopsy tissue from a Swedish cohort of men with prostate cancer (UPCA, n = 100). The primary outcome of adverse pathology and secondary outcomes of high primary Gleason (≥G4) and high pathological T‐stage (≥T3) were assessed by likelihood ratio statistics and area under the receiver operating characteristic curves from logistic regression models; time to biochemical recurrence was assessed by likelihood ratio statistics and C‐indexes from Cox proportional hazard regression models. Results Biopsy MCRS was significantly prognostic (p < 0.0001) and added significant prognostic value to clinico‐pathological features for adverse pathology, high primary Gleason and high pathological T‐stage (p < 0.0001). MCRS was prognostic for biochemical recurrence and added some, albeit non‐significant, prognostic value to clinical risk stratifiers, which could reflect the low number of recurrence events in the cohort. Conclusion Biopsy‐based MCRS improves risk stratification over standard clinical and pathological information and optimises patient management after diagnosis of prostate cancer.https://doi.org/10.1002/bco2.474gene expression signaturemolecular risk scorepatient managementprognosisprostate cancerrisk stratification
spellingShingle Agnieszka Krzyzanowska
Debra F. Higgins
Stephen Barron
Tony Loughman
Amanda O'Neill
Katherine M. Sheehan
Chan‐Ju Angel Wang
Bozena Fender
Leah McGuire
Joanna Fay
Anthony O'Grady
Des O'Leary
R. William Watson
Anders Bjartell
William M. Gallagher
Clinical validation of a biopsy‐based six‐gene signature prognostic for aggressive prostate cancer
BJUI Compass
gene expression signature
molecular risk score
patient management
prognosis
prostate cancer
risk stratification
title Clinical validation of a biopsy‐based six‐gene signature prognostic for aggressive prostate cancer
title_full Clinical validation of a biopsy‐based six‐gene signature prognostic for aggressive prostate cancer
title_fullStr Clinical validation of a biopsy‐based six‐gene signature prognostic for aggressive prostate cancer
title_full_unstemmed Clinical validation of a biopsy‐based six‐gene signature prognostic for aggressive prostate cancer
title_short Clinical validation of a biopsy‐based six‐gene signature prognostic for aggressive prostate cancer
title_sort clinical validation of a biopsy based six gene signature prognostic for aggressive prostate cancer
topic gene expression signature
molecular risk score
patient management
prognosis
prostate cancer
risk stratification
url https://doi.org/10.1002/bco2.474
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