Circulating cell-free AR and CYP17A1 copy number variations may associate with outcome of metastatic castration-resistant prostate cancer patients treated with abiraterone

Br J Cancer. 2015 May 12;112(10):1717-24. doi: 10.1038/bjc.2015.128. Epub 2015 Apr 21.

Abstract

Background: This study aimed to investigate copy number variations (CNVs) of CYP17A1 and androgen receptor (AR) genes in serum cell-free DNA collected before starting abiraterone in 53 consecutive patients with castration-resistant prostate cancer (CRPC).

Methods: Serum DNA was isolated and CNVs were analysed for AR and CYP17A1 genes using Taqman copy number assays. The association between CNVs and progression-free/overall survival (PFS/OS) was evaluated by the Kaplan-Meier method and log-rank test.

Results: Median PFS of patients with AR gene gain was 2.8 vs 9.5 months of non-gained cases (P < 0.0001). Patients with CYP17A1 gene gain had a median PFS of 2.8 months vs 9.2 months in the non-gained patients (P = 0.0014). A lower OS was reported in both cases (AR: P < 0.0001; CYP17A1: P = 0.0085). Multivariate analysis revealed that PSA decline ⩾ 50%, AR and CYP17A1 CNVs were associated with shorter PFS (P < 0.0001, P = 0.0004 and P = 0.0450, respectively), while performance status, PSA decline ⩾ 50%, AR CNV and DNA concentration were associated with OS (P = 0.0021, P = 0.0014, P = 0.0026 and P = 0.0129, respectively).

Conclusions: CNVs of AR and CYP17A1 genes would appear to be associated with outcome of CRPC patients treated with abiraterone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Androstenes / therapeutic use*
  • Case-Control Studies
  • DNA / genetics
  • DNA Copy Number Variations*
  • Disease-Free Survival
  • Humans
  • Kallikreins / blood
  • Male
  • Middle Aged
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms, Castration-Resistant / blood
  • Prostatic Neoplasms, Castration-Resistant / drug therapy*
  • Prostatic Neoplasms, Castration-Resistant / enzymology
  • Prostatic Neoplasms, Castration-Resistant / genetics*
  • Receptors, Androgen / blood*
  • Receptors, Androgen / genetics
  • Retrospective Studies
  • Steroid 17-alpha-Hydroxylase / blood*
  • Steroid 17-alpha-Hydroxylase / genetics

Substances

  • AR protein, human
  • Androstenes
  • Receptors, Androgen
  • DNA
  • CYP17A1 protein, human
  • Steroid 17-alpha-Hydroxylase
  • Kallikreins
  • kallikrein-related peptidase 3, human
  • Prostate-Specific Antigen
  • abiraterone