title: Prognostic significance of circulating intact and cleaved forms of urokinase plasminogen activator receptor in inoperable chemotherapy treated cholangiocarcinoma patients.
abstract: BACKGROUND
  High levels of intact and cleaved forms of the urokinase-type plasminogen activator receptor (uPAR) in both tissue and blood are associated with poor survival in several cancer diseases. The prognostic significance of uPAR in cholangiocarcinoma is unknown. The aims of this study were to determine if pre-treatment serum levels of uPAR forms and a decrease in levels during chemotherapy are predictive of survival in patients with inoperable cholangiocarcinoma.
  
  
  METHODS
  Patients with inoperable cholangiocarcinoma were consecutively included in the training set (n=108). A test set included patients from a different hospital using similar treatment guidelines (n=60). Serum levels of the different uPAR forms were determined using time-resolved fluorescence immunoassays (TR-FIA). The Cox proportional hazards model was used for the uni- and multivariate survival analyses.
  
  
  RESULTS
  Baseline level of uPAR(I-III)+uPAR(II-III) was an independent predictor of survival (HR=2.08, 95% CI:1.46-2.97, p<0.0001). Applying the linear predictor from the training set to the test set, it was validated that uPAR(I-III)+uPAR(II-III) predicted overall survival (p=0.049). A high level of uPAR(I-III)+uPAR(II-III) after 2cycles of chemotherapy was associated with poor survival (HR=1.79, 95% CI:1.08-2.97, p=0.023, n=57). This predictor, however, was not significant in the test set (p=0.21, 26 events in 27 patients).
  
  
  CONCLUSIONS
  The baseline level of uPAR(I-III)+uPAR(II-III) is a predictor of survival in inoperable cholangiocarcinoma patients.
authors: Dept. of Oncology, Rigshospitalet, DK-2100 Copenhagen Ø, Denmark. Electronic address: mie.grunnet.knudsen@regionh.dk.
authors: M
authors: M
authors: Grunnet
authors: The Finsen Laboratory, Rigshospitalet & Biotech Research and Innovation Centre, University of Copenhagen, DK-2200 Copenhagen N, Denmark. Electronic address: ib.jarle.christensen@regionh.dk.
authors: I J
authors: IJ
authors: Christensen
authors: Dept. of Oncology, Rigshospitalet, DK-2100 Copenhagen Ø, Denmark. Electronic address: ulrik.lassen@regionh.dk.
authors: U
authors: U
authors: Lassen
authors: Dept. Of Oncology, Lillebælt Hospital Vejle, DK-7100 Vejle, Denmark. Electronic address: lars.henrik.jensen@slb.regionsyddanmark.dk.
authors: L H
authors: LH
authors: Jensen
authors: Dept. Of Clinical biochemistry and Immunology, National Institute for Health Data and Disease Control, DK-2300 Copenhagen S, Denmark. Electronic address: mlp@ssi.dk.
authors: M
authors: M
authors: Lydolph
authors: The Finsen Laboratory, Rigshospitalet & Biotech Research and Innovation Centre, University of Copenhagen, DK-2200 Copenhagen N, Denmark. Electronic address: ikl@finsenlab.dk.
authors: I K
authors: IK
authors: Lund
authors: The Finsen Laboratory, Rigshospitalet & Biotech Research and Innovation Centre, University of Copenhagen, DK-2200 Copenhagen N, Denmark. Electronic address: tinets@finsenlab.dk.
authors: T
authors: T
authors: Thurison
authors: The Finsen Laboratory, Rigshospitalet & Biotech Research and Innovation Centre, University of Copenhagen, DK-2200 Copenhagen N, Denmark. Electronic address: gunilla@finsenlab.dk.
authors: G
authors: G
authors: Høyer-Hansen
authors: Dept. of Oncology, Rigshospitalet, DK-2100 Copenhagen Ø, Denmark. Electronic address: morten.mau.soerensen@regionh.dk.
authors: M
authors: M
authors: Mau-Sørensen
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism; D018281:Cholangiocarcinoma / Q000097:blood* / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D055293:Receptors, Urokinase Plasminogen Activator / Q000097:blood* / Q000378:metabolism*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D055293:Receptors, Urokinase Plasminogen Activator
keywords: Cholangiocarcinoma; Prognostic marker; Urokinase plasminogen activator receptor