title: Plasma osteopontin as a biomarker of prostate cancer aggression: relationship to risk category and treatment response.
abstract: BACKGROUND
  High plasma osteopontin (OPN) has been linked to tumour hypoxia, metastasis, and poor prognosis. This study aims to assess whether plasma osteopontin was a biomarker of increasing progression within prostate cancer (PCa) prognostic groups and whether it reflected treatment response to local and systemic therapies.
  
  
  METHODS
  Baseline OPN was determined in men with localised (n=199), locally recurrent (n=9) and castrate-resistant, metastatic PCa (CRPC-MET; n=37). Receiver-operating curves (ROC) were generated to describe the accuracy of OPN for distinguishing between localised risk groups or localised vs metastatic disease. We also measured OPN pre- and posttreatment, following radical prostatectomy, external beam radiotherapy (EBRT), androgen deprivation (AD) or taxane-based chemotherapy.
  
  
  RESULTS
  The CRPC-MET patients had increased baseline values (mean 219; 56-513 ng ml(-1); P<0.0001) compared with the localised, non-metastatic group (mean 72; 12-438 ng ml(-1)). The area under the ROC to differentiate localised vs metastatic disease was improved when OPN was added to prostate-specific antigen (PSA) (0.943-0.969). Osteopontin neither distinguished high-risk PCa from other localised PCa nor correlated with serum PSA at baseline. Osteopontin levels reduced in low-risk patients after radical prostatectomy (P=0.005) and in CRPC-MET patients after chemotherapy (P=0.027), but not after EBRT or AD.
  
  
  CONCLUSIONS
  Plasma OPN is as good as PSA at predicting treatment response in CRPC-MET patients after chemotherapy. Our data do not support the use of plasma OPN as a biomarker of increasing tumour burden within localised PCa.
authors.affiliation: Departments of Radiation Oncology, Surgery and Biostatistics, University of Toronto and Ontario Cancer Institute/Princess Margaret Hospital (University Health Network), Toronto, Ontario, Canada.
authors.forename: J W
authors.initials: JW
authors.lastname: Thoms
authors.forename: A
authors.initials: A
authors.lastname: Dal Pra
authors.forename: P H
authors.initials: PH
authors.lastname: Anborgh
authors.forename: E
authors.initials: E
authors.lastname: Christensen
authors.forename: N
authors.initials: N
authors.lastname: Fleshner
authors.forename: C
authors.initials: C
authors.lastname: Menard
authors.forename: K
authors.initials: K
authors.lastname: Chadwick
authors.forename: M
authors.initials: M
authors.lastname: Milosevic
authors.forename: C
authors.initials: C
authors.lastname: Catton
authors.forename: M
authors.initials: M
authors.lastname: Pintilie
authors.forename: A F
authors.initials: AF
authors.lastname: Chambers
authors.forename: R G
authors.initials: RG
authors.lastname: Bristow
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D018450:Disease Progression; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000473:pathology / Q000628:therapy; D053495:Osteopontin / Q000097:blood*; D011379:Prognosis; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000097:blood* / Q000473:pathology / Q000628:therapy; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; D053495:Osteopontin