title: Serum levels of arachidonic acid metabolites change during prostate cancer progression.
abstract: BACKGROUND
  Arachidonic acid (AA) pathway has been shown to play a role in the development and progression of prostate cancer (PCa). In this study we aimed to assess the changes in concentrations of hydroxyeicosatetraenoic acids (HETEs) in serum samples from patients diagnosed with PCa compared to controls.
  
  
  METHODS
  HETEs were determined using ultrahigh pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS).
  
  
  RESULTS
  Elevated concentrations of 5-HETE, 8-HETE, 11-HETE and 15-HETE were observed in 6 out of 20 patients diagnosed with PCa; no statistical differences with controls were observed for 12-HETE and AA in the discovery set. An independent validation set composed of 222 samples divided in five groups ranging from subjects with low PSA and no PCa, to patients with advanced PCa was included. In 30% of the patients in the advanced PCa group, up to ten times higher concentrations of the same set of HETEs were observed with a significant concomitant decrease of the concentration of AA. Logistic regression and Kaplan-Meier curves illustrate that a decreased concentration of AA is a predictor of PCa biochemical recurrence after radical prostatectomy (RP).
  
  
  CONCLUSIONS
  From the present study we conclude that a significant association between AA and AA metabolites in serum and PCa progression exists, although serum concentrations of HETEs exhibited low sensitivity toward the diagnosis of PCa.
authors.affiliation: Department of Neurology, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Giovanny
authors.initials: G
authors.lastname: Rodríguez-Blanco
authors.forename: Peter C
authors.initials: PC
authors.lastname: Burgers
authors.forename: Lennard J M
authors.initials: LJ
authors.lastname: Dekker
authors.forename: Jan J N
authors.initials: JJ
authors.lastname: Ijzermans
authors.forename: Mark F
authors.initials: MF
authors.lastname: Wildhagen
authors.forename: Ellen A M
authors.initials: EA
authors.lastname: Schenk-Braat
authors.forename: Chris H
authors.initials: CH
authors.lastname: Bangma
authors.forename: Guido
authors.initials: G
authors.lastname: Jenster
authors.forename: Theo M
authors.initials: TM
authors.lastname: Luider
mesh_terms: D000368:Aged; D016718:Arachidonic Acid / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D018450:Disease Progression; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000097:blood* / Q000473:pathology; D053719:Tandem Mass Spectrometry
chemical_list: D006893:Hydroxyeicosatetraenoic Acids; D016718:Arachidonic Acid
keywords: HETEs; UHPLC; arachidonic acid; biomarker; mass spectrometry; prostate cancer