title: AR-V7 Transcripts in Whole Blood RNA of Patients with Metastatic Castration Resistant Prostate Cancer Correlate with Response to Abiraterone Acetate.
abstract: The expression of AR-V7 (androgen receptor splice variant) 7 in circulating tumor cells has been associated with resistance to abiraterone and enzalutamide in patients with metastatic castration resistant prostate cancer. We used a sensitive, whole blood reverse transcriptase-polymerase chain reaction assay that does not require circulating tumor cell enrichment to correlate outcomes of abiraterone with whole blood expression of AR-V7 and other prostate cancer associated transcripts.
  
  
  
  We assessed the expression of AR-V7, FOXA1, GRHL2, HOXB13, KLK2, KLK3 and TMPRSS2:ERG mRNA in 2.5 ml whole blood from each of 27 patients with metastatic castration resistant prostate cancer and 33 controls without cancer as the discovery cohort. Cycle threshold values of controls with the highest gene expression were set as the threshold for a positive test. Thresholds were then applied to a validation cohort of 37 patients with metastatic castration resistant prostate cancer who were commencing abiraterone. Gene expression was correlated with the prostate specific antigen response rate using the chi-square test, and with time to prostate specific antigen progression and overall survival using the log rank test.
  
  
  
  In the discovery cohort 3 of 27 patients (11.1%) with metastatic castration resistant prostate cancer were AR-V7 positive vs 4 of 37 (10.8%) in the validation cohort. In the validation cohort patients with a positive AR-V7 test had a lower prostate specific antigen response rate (0% vs 42%, p = 0.27) together with shorter median prostate specific antigen progression (0.7 vs 4.0 months, p <0.001) and median overall survival (5.5 vs 22.1 months, p <0.001).
  
  
  
  Reverse transcriptase-polymerase chain reaction detection of AR-V7 transcripts in whole blood was associated with inferior outcomes in patients treated with abiraterone. These results reinforce the potential usefulness of AR-V7 as a prognostic and predictive biomarker for metastatic castration resistant prostate cancer.
authors.affiliation: Vancouver Prostate Centre, University of British Columbia, British Columbia, Vancouver, Canada; Department of Urology, University Hospital, Tübingen, Germany.
authors.forename: Tilman
authors.initials: T
authors.lastname: Todenhöfer
authors.affiliation: British Columbia Cancer Agency, British Columbia, Vancouver, Canada; Department of Medicine, Monash University, Melbourne, Victoria, Australia.
authors.forename: Arun
authors.initials: A
authors.lastname: Azad
authors.affiliation: Vancouver Prostate Centre, University of British Columbia, British Columbia, Vancouver, Canada.
authors.forename: Craig
authors.initials: C
authors.lastname: Stewart
authors.affiliation: Vancouver Prostate Centre, University of British Columbia, British Columbia, Vancouver, Canada.
authors.forename: Jian
authors.initials: J
authors.lastname: Gao
authors.affiliation: British Columbia Cancer Agency, British Columbia, Vancouver, Canada.
authors.forename: Bernhard J
authors.initials: BJ
authors.lastname: Eigl
authors.affiliation: Vancouver Prostate Centre, University of British Columbia, British Columbia, Vancouver, Canada.
authors.forename: Martin E
authors.initials: ME
authors.lastname: Gleave
authors.affiliation: Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Joshua
authors.affiliation: Vancouver Prostate Centre, University of British Columbia, British Columbia, Vancouver, Canada.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Black
authors.affiliation: Vancouver Prostate Centre, University of British Columbia, British Columbia, Vancouver, Canada; British Columbia Cancer Agency, British Columbia, Vancouver, Canada. Electronic address: kchi@bccancer.bc.ca.
authors.forename: Kim N
authors.initials: KN
authors.lastname: Chi
mesh_terms: D000367:Age Factors; D000368:Aged; D000704:Analysis of Variance; D000736:Androstenes / Q000008:administration & dosage*; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D018572:Disease-Free Survival; D006801:Humans; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D012333:RNA, Messenger / Q000235:genetics; D011944:Receptors, Androgen / Q000235:genetics*; D015203:Reproducibility of Results; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: C410798:AR protein, human; D000736:Androstenes; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D011944:Receptors, Androgen; D017430:Prostate-Specific Antigen; C089740:abiraterone
keywords: abiraterone; androgen; biomarkers; castration-resistant; neoplasm metastasis; prostatic neoplasms; receptors; tumor