title: KLK3, PCA3, and TMPRSS2-ERG expression in the peripheral blood mononuclear cell fraction from castration-resistant prostate cancer patients and response to docetaxel treatment.
abstract: BACKGROUND
  To monitor systemic disease activity, the potential of circulating tumor cells (CTCs) bears great promise. As surrogate for CTCs we measured KLK3, PCA3, and TMPRSS2-ERG messenger RNA (mRNA) in the peripheral blood mononuclear cell (PBMC) fraction from a castration-resistant prostate cancer (CRPC) patient cohort and three control groups. Moreover, biomarker response to docetaxel treatment was evaluated in the patient group.
  
  
  METHODS
  Blood samples from 20 CRPC patients were analyzed at four different time points (prior to docetaxel treatment, at 9 weeks, 27 weeks, and 2 months after treatment). Blood was drawn once from three control groups (10 age-matched men, 10 men under 35 years of age, 12 women). All samples were analyzed for KLK3, PCA3, and TMPRSS2-ERG mRNA by using a quantitative nucleic acid amplification assay with gene-specific primers in the complementary DNA synthesis.
  
  
  RESULTS
  At baseline, mRNA for KLK3 was detected in 17 (89%, 95% CI 76-100%), PCA3 in 10 (53%, 95% CI 30-75%), and TMPRSS2-ERG in seven of 19 evaluable patients (37%, 95% CI 15-59%). In contrast, the blood samples from all 32 healthy volunteers were reproducible negative for all markers. In response to docetaxel treatment, KLK3 levels decreased in 80% (95% CI 60-100%), PCA3 in 89% (95% CI 68-100%), and TMPRSS2-ERG in 86% (95% CI 60-100%) of patients.
  
  
  CONCLUSIONS
  The feasibility of a highly sensitive modified nucleic acid amplification assay to assess KLK3, PCA3, and TMPRSS2-ERG mRNA in the PBMC fraction from CRPC patients was demonstrated. Moreover, response of these markers to systemic treatment was shown.
authors.affiliation: Department of Urology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Siebren
authors.initials: S
authors.lastname: Dijkstra
authors.forename: Gisele H J M
authors.initials: GH
authors.lastname: Leyten
authors.forename: Sander A
authors.initials: SA
authors.lastname: Jannink
authors.forename: Hans
authors.initials: H
authors.lastname: de Jong
authors.forename: Peter F A
authors.initials: PF
authors.lastname: Mulders
authors.forename: Inge M
authors.initials: IM
authors.lastname: van Oort
authors.forename: Jack A
authors.initials: JA
authors.lastname: Schalken
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D000077143:Docetaxel; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007610:Kallikreins / Q000096:biosynthesis / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis / Q000235:genetics*; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000096:biosynthesis / Q000235:genetics*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D043823:Taxoids / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; C515553:TMPRSS2-ERG fusion protein, human; D043823:Taxoids; C479341:prostate cancer antigen 3, human; D000077143:Docetaxel; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: CTC; biomarkers; circulating tumor cells