title: Circulating intact and cleaved forms of the urokinase-type plasminogen activator receptor: biological variation, reference intervals and clinical useful cut-points.
abstract: BACKGROUND
  High levels of circulating forms of the urokinase-type plasminogen activator receptor (uPAR) are significantly associated to poor prognosis in cancer patients. Our aim was to determine biological variations and reference intervals of the uPAR forms in blood, and in addition, to test the clinical relevance of using these as cut-points in colorectal cancer (CRC) prognosis.
  
  
  METHODS
  uPAR forms were measured in citrated and EDTA plasma samples using time-resolved fluorescence immunoassays. Diurnal, intra- and inter-individual variations were assessed in plasma samples from cohorts of healthy individuals. Reference intervals were determined in plasma from healthy individuals randomly selected from a Danish multi-center cross-sectional study. A cohort of CRC patients was selected from the same cross-sectional study.
  
  
  RESULTS
  The reference intervals showed a slight increase with age and women had ~20% higher levels. The intra- and inter-individual variations were ~10% and ~20-30%, respectively and the measured levels of the uPAR forms were within the determined 95% reference intervals. No diurnal variation was found. Applying the normal upper limit of the reference intervals as cut-point for dichotomizing CRC patients revealed significantly decreased overall survival of patients with levels above this cut-point of any uPAR form.
  
  
  CONCLUSIONS
  The reference intervals for the different uPAR forms are valid and the upper normal limits are clinically relevant cut-points for CRC prognosis.
authors.affiliation: The Finsen Laboratory, Copenhagen University Hospital, DK-2200 Copenhagen, Denmark; Biotech Research & Innovation Centre (BRIC), University of Copenhagen, DK-2200 Copenhagen, Denmark. Electronic address: tinets@finsenlab.dk.
authors.forename: Tine
authors.initials: T
authors.lastname: Thurison
authors.affiliation: The Finsen Laboratory, Copenhagen University Hospital, DK-2200 Copenhagen, Denmark; Biotech Research & Innovation Centre (BRIC), University of Copenhagen, DK-2200 Copenhagen, Denmark.
authors.forename: Ib J
authors.initials: IJ
authors.lastname: Christensen
authors.affiliation: The Finsen Laboratory, Copenhagen University Hospital, DK-2200 Copenhagen, Denmark; Biotech Research & Innovation Centre (BRIC), University of Copenhagen, DK-2200 Copenhagen, Denmark.
authors.forename: Ida K
authors.initials: IK
authors.lastname: Lund
authors.affiliation: Department of Surgical Gastroenterology, Hvidovre Hospital, DK-2650 Hvidovre, Denmark.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Nielsen
authors.affiliation: The Finsen Laboratory, Copenhagen University Hospital, DK-2200 Copenhagen, Denmark; Biotech Research & Innovation Centre (BRIC), University of Copenhagen, DK-2200 Copenhagen, Denmark.
authors.forename: Gunilla
authors.initials: G
authors.lastname: Høyer-Hansen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D015200:Fluoroimmunoassay / Q000592:standards; D006801:Humans; D008297:Male; D008875:Middle Aged; D055293:Receptors, Urokinase Plasminogen Activator / Q000097:blood* / Q000737:chemistry*; D012016:Reference Values; D013997:Time Factors; D055815:Young Adult
chemical_list: D055293:Receptors, Urokinase Plasminogen Activator
keywords: Age- and gender-dependent variation; Cancer biomarker; Colorectal cancer; Reference intervals; Time-resolved fluorescence immunoassay; Urokinase receptor