title: Development of a label-free LC-MS/MS strategy to approach the identification of candidate protein biomarkers of disease recurrence in prostate cancer patients in a clinical trial of combined hormone and radiation therapy.
abstract: OBJECTIVE
  Combined hormone and radiation therapy (CHRT) is one of the principle curative regimes for localised prostate cancer (PCa). Following treatment, many patients subsequently experience disease recurrence however; current diagnostics tests fail to predict the onset of disease recurrence. Biomarkers that address this issue would be of significant advantage.
  
  
  METHODS
  Label-free LC-MS/MS for protein biomarker discovery and MRM for targeted confirmation were applied to patient serum samples accrued in a non-interventional clinical trial of CHRT.
  
  
  RESULTS
  Analysis of time-matched patient samples from a patient with disease recurrence compared with a time match disease-free individual supported the identification of 287 proteins. Of these, 141 proteins were quantified, 95 proteins changed in their expression (P ≤ 0.05 and ≥1.5-fold change) and of these 16 were selected for MRM confirmation. The protein expression changes observed in the label-free LC-MS/MS and MRM analysis were found to be highly correlated (R(2) = 0.85).
  
  
  CONCLUSIONS
  The establishment of a clinical trial to support the acquisition of samples and development of a pipeline for MS-based biomarker discovery and validation should contribute to the identification of a serum protein signature to predict or monitor the outcome of treatment of patients with PCa.
authors.affiliation: Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland.
authors.forename: Brian
authors.initials: B
authors.lastname: Morrissey
authors.forename: Carmel
authors.initials: C
authors.lastname: O'Shea
authors.forename: John
authors.initials: J
authors.lastname: Armstrong
authors.forename: Cathy
authors.initials: C
authors.lastname: Rooney
authors.forename: Lisa
authors.initials: L
authors.lastname: Staunton
authors.forename: Martina
authors.initials: M
authors.lastname: Sheehan
authors.forename: Aoife M
authors.initials: AM
authors.lastname: Shannon
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Pennington
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D001798:Blood Proteins / Q000032:analysis / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003131:Combined Modality Therapy; D006801:Humans; D008297:Male; D036103:Nanotechnology; D025341:Principal Component Analysis; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy; D012008:Recurrence; D053719:Tandem Mass Spectrometry; D013997:Time Factors; D014357:Trypsin / Q000378:metabolism
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D001798:Blood Proteins; D014357:Trypsin