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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.
- 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