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Prognostic Utility of a Whole-blood Androgen Receptor-based Gene Signature in Metastatic Castration-resistant Prostate Cancer.

Prognostic Utility of a Whole-blood Androgen Receptor-based Gene Signature in Metastatic Castration-resistant Prostate Cancer.

Authors :
Fettke H.
Docanto M.M.
To S.Q.
Bukczynska P.
Mant A.
Pook D.
Ng N.
Graham L.-J.K.
Mangiola S.
Segelov E.
Mahon K.
Davis I.D.
Parente P.
Pezaro C.
Todenhofer T.
Horvath L.G.
Azad A.A.
Kwan E.M.
Fettke H.
Docanto M.M.
To S.Q.
Bukczynska P.
Mant A.
Pook D.
Ng N.
Graham L.-J.K.
Mangiola S.
Segelov E.
Mahon K.
Davis I.D.
Parente P.
Pezaro C.
Todenhofer T.
Horvath L.G.
Azad A.A.
Kwan E.M.
Publication Year :
2019

Abstract

Background: The treatment paradigm for metastatic castration-resistant prostate cancer (mCRPC) has evolved significantly in recent years. Identifying predictive and/or prognostic biomarkers in the context of this rapidly expanding therapeutic armamentarium remains a pressing and unmet clinical need. Objective(s): To develop a prognostic whole-blood gene signature for mCRPC patients. Design, setting, and participants: As part of an ongoing prospective, multicentre biomarker research study (Australian Prostate Biomarker Alliance), we enrolled 115 mCRPC patients commencing chemotherapy (n = 34) or androgen receptor (AR) pathway inhibitors therapy (n = 81) and obtained pretreatment whole-blood samples in PAXgene RNA tubes. Gene expression was assessed using reverse transcription-polymerase chain reaction. Outcome measurements and statistical analysis: Gene transcripts correlating with overall survival (OS) at p < 0.10 in univariate Cox regression models were incorporated into a multigene signature. Kaplan-Meier survival estimates and multivariate analyses were used to assess association with clinical outcomes. Prognostic strength of the signature was estimated using a concordance probability estimate (CPE). Results and limitations: Based on univariate analysis for OS, the following genes were incorporated into a multigene signature: AR splice variant 7 (AR-V7), and three androgen-regulated genes: GRHL2, HOXB13, and FOXA1. The number of positive transcripts clearly stratified survival outcomes (median OS: not reached vs 24.8 mo vs 16.2 mo for 0, 1, and >=2 transcripts, respectively; p = 0.0052). Notably, this multigene signature retained prognostic significance on multivariable analysis (hazard ratio, 2.1; 95% confidence interval, 1.1-4.0; p = 0.019). Moreover, CPE for this model was 0.78, indicating strong discriminative capacity. Limitations include short follow-up time. Conclusion(s): Our data demonstrate the prognostic utility of a novel whole-blood AR-based signatur<br />We demonstrated that a whole-blood androgen receptor-based multigene signature was an important prognostic tool in a cohort of metastatic castration-resistant prostate cancer (mCRPC)patients receiving contemporaneous systemic treatment. This signature may have a valuable role in upfront risk stratification and prognostication of mCRPC patients. Background: The treatment paradigm for metastatic castration-resistant prostate cancer (mCRPC)has evolved significantly in recent years. Identifying predictive and/or prognostic biomarkers in the context of this rapidly expanding therapeutic armamentarium remains a pressing and unmet clinical need. Objective(s): To develop a prognostic whole-blood gene signature for mCRPC patients. Design, setting, and participants: As part of an ongoing prospective, multicentre biomarker research study (Australian Prostate Biomarker Alliance), we enrolled 115 mCRPC patients commencing chemotherapy (n = 34)or androgen receptor (AR)pathway inhibitors therapy (n = 81)and obtained pretreatment whole-blood samples in PAXgene RNA tubes. Gene expression was assessed using reverse transcription-polymerase chain reaction. Outcome measurements and statistical analysis: Gene transcripts correlating with overall survival (OS)at p < 0.10 in univariate Cox regression models were incorporated into a multigene signature. Kaplan-Meier survival estimates and multivariate analyses were used to assess association with clinical outcomes. Prognostic strength of the signature was estimated using a concordance probability estimate (CPE). Results and limitations: Based on univariate analysis for OS, the following genes were incorporated into a multigene signature: AR splice variant 7 (AR-V7), and three androgen-regulated genes: GRHL2, HOXB13, and FOXA1. The number of positive transcripts clearly stratified survival outcomes (median OS: not reached vs 24.8 mo vs 16.2 mo for 0, 1, and >=2 transcripts, respectively; p = 0.0052). Notably, this multigene signature retain

Details

Database :
OAIster
Publication Type :
Electronic Resource
Accession number :
edsoai.on1305120884
Document Type :
Electronic Resource