title: Phase 2 study of circulating microRNA biomarkers in castration-resistant prostate cancer.
abstract: BACKGROUND
  Biomarkers of therapeutic response and prognosis are needed to assist in the sequencing of treatments for metastatic castration-resistant prostate cancer (CRPC). Previously in a Phase 1 discovery study, we identified 14 circulating microRNAs that were associated with response to docetaxel chemotherapy or overall survival. We performed a Phase 2 validation study to verify these findings.
  
  
  METHODS
  Using real-time PCR, the levels of the 14 microRNAs were measured in plasma collected before and after the first cycle of docetaxel from a Phase 2 cohort of 89 patients.
  
  
  RESULTS
  The microRNAs were not associated with docetaxel response in the Phase 2 cohort. Higher baseline levels of six microRNAs, predominantly of the miR-200 family, were confirmed to be associated with shorter overall survival. A microRNA signature comprising these six microRNAs predicted high-risk patients in the Phase 2 cohort with a hazard ratio of 4.12 (95% CI 2.20-7.70, P=0.000001). The signature was an independent predictor in multivariable analysis with clinicopathological factors.
  
  
  CONCLUSIONS
  The association of circulating microRNAs with overall survival suggests their involvement in CRPC progression.
authors.affiliation: Cancer Division, The Kinghorn Cancer Centre/Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.|St Vincent's Clinical School, Faculty of Medicine, The University of New South Wales, Darlinghurst, New South Wales 2010, Australia.
authors.forename: Hui-Ming
authors.initials: HM
authors.lastname: Lin
authors.affiliation: Cancer Division, The Kinghorn Cancer Centre/Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.|St Vincent's Clinical School, Faculty of Medicine, The University of New South Wales, Darlinghurst, New South Wales 2010, Australia.|Department of Medical Oncology, Chris O'Brien Lifehouse, Camperdown, New South Wales 2050, Australia.|Royal Prince Alfred Hospital, Camperdown, New South Wales 2050, Australia.
authors.forename: Kate L
authors.initials: KL
authors.lastname: Mahon
authors.affiliation: Cancer Division, The Kinghorn Cancer Centre/Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.
authors.forename: Calan
authors.initials: C
authors.lastname: Spielman
authors.affiliation: Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, New South Wales 2145, Australia.|Pharmacogenomics Research for Individualised Medicine (PRIMe) consortium, New South Wales, Australia.
authors.forename: Howard
authors.initials: H
authors.lastname: Gurney
authors.affiliation: Pharmacogenomics Research for Individualised Medicine (PRIMe) consortium, New South Wales, Australia.|Calvary Mater Newcastle Hospital, Waratah, New South Wales 2298, Australia.
authors.forename: Girish
authors.initials: G
authors.lastname: Mallesara
authors.affiliation: Department of Medical Oncology, Chris O'Brien Lifehouse, Camperdown, New South Wales 2050, Australia.|Royal Prince Alfred Hospital, Camperdown, New South Wales 2050, Australia.|Pharmacogenomics Research for Individualised Medicine (PRIMe) consortium, New South Wales, Australia.|Sydney Medical School, University of Sydney, Camperdown, New South Wales 2050, Australia.|Concord Repatriation General Hospital, Concord, New South Wales 2139, Australia.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Stockler
authors.affiliation: Pharmacogenomics Research for Individualised Medicine (PRIMe) consortium, New South Wales, Australia.|St George Hospital, Kogarah, New South Wales 2217, Australia.
authors.forename: Patricia
authors.initials: P
authors.lastname: Bastick
authors.affiliation: Pharmacogenomics Research for Individualised Medicine (PRIMe) consortium, New South Wales, Australia.|Mid North Coast Cancer Institute, Coffs Harbour Health Campus, Coffs Harbour, New South Wales 2450, Australia.
authors.forename: Karen
authors.initials: K
authors.lastname: Briscoe
authors.affiliation: Pharmacogenomics Research for Individualised Medicine (PRIMe) consortium, New South Wales, Australia.|Sydney Adventist Hospital, Wahroonga, New South Wales 2076, Australia.
authors.forename: Gavin
authors.initials: G
authors.lastname: Marx
authors.affiliation: Cancer Division, The Kinghorn Cancer Centre/Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.|St Vincent's Clinical School, Faculty of Medicine, The University of New South Wales, Darlinghurst, New South Wales 2010, Australia.
authors.forename: Alexander
authors.initials: A
authors.lastname: Swarbrick
authors.affiliation: Cancer Division, The Kinghorn Cancer Centre/Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.|St Vincent's Clinical School, Faculty of Medicine, The University of New South Wales, Darlinghurst, New South Wales 2010, Australia.|Department of Medical Oncology, Chris O'Brien Lifehouse, Camperdown, New South Wales 2050, Australia.|Royal Prince Alfred Hospital, Camperdown, New South Wales 2050, Australia.|Pharmacogenomics Research for Individualised Medicine (PRIMe) consortium, New South Wales, Australia.|Sydney Medical School, University of Sydney, Camperdown, New South Wales 2050, Australia.
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Horvath
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D017321:Clinical Trials, Phase I as Topic; D015331:Cohort Studies; D018450:Disease Progression; D000077143:Docetaxel; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D015996:Survival Rate; D043823:Taxoids / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D035683:MicroRNAs; D043823:Taxoids; D000077143:Docetaxel