title: Quantification of a proteotypic peptide from protein C inhibitor by liquid chromatography-free SISCAPA-MALDI mass spectrometry: application to identification of recurrence of prostate cancer.
abstract: BACKGROUND
  Biomarker validation remains one of the most challenging constraints to the development of new diagnostic assays. To facilitate biomarker validation, we previously developed a chromatography-free stable isotope standards and capture by antipeptide antibodies (SISCAPA)-MALDI assay allowing rapid, high-throughput quantification of protein analytes in large sample sets. Here we applied this assay to the measurement of a surrogate proteotypic peptide from protein C inhibitor (PCI) in sera from patients with prostate cancer.
  
  
  METHODS
  A 2-plex SISCAPA-MALDI assay for quantification of proteotypic peptides from PCI and soluble transferrin receptor (sTfR) was used to measure these peptides in 159 trypsin-digested sera collected from 51 patients with prostate cancer. These patients had been treated with radiation with or without neoadjuvant androgen deprivation.
  
  
  RESULTS
  Patients who experienced biochemical recurrence of prostate cancer showed decreased serum concentrations of the PCI peptide analyte within 18 months of treatment. The PCI peptide concentrations remained increased in the sera of patients who did not experience cancer recurrence. Prostate-specific antigen concentrations had no predictive value during the same time period.
  
  
  CONCLUSIONS
  The high-throughput, liquid chromatography-free SISCAPA-MALDI assay is capable of rapid quantification of proteotypic PCI and sTfR peptide analytes in complex serum samples. Decreased serum concentrations of the PCI peptide were found to be related to recurrence of prostate cancer in patients treated with radiation with or without hormone therapy. However, a larger cohort of patients will be required for unequivocal validation of the PCI peptide as a biomarker for clinical use.
authors.affiliation: Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada;
authors.forename: Morteza
authors.initials: M
authors.lastname: Razavi
authors.forename: Lisa D S
authors.initials: LD
authors.lastname: Johnson
authors.forename: Julian J
authors.initials: JJ
authors.lastname: Lum
authors.forename: Gary
authors.initials: G
authors.lastname: Kruppa
authors.forename: N Leigh
authors.initials: NL
authors.lastname: Anderson
authors.forename: Terry W
authors.initials: TW
authors.lastname: Pearson
mesh_terms: D000726:Androgen Antagonists / Q000627:therapeutic use; D057166:High-Throughput Screening Assays; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009364:Neoplasm Recurrence, Local; D010455:Peptides / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy / Q000532:radiotherapy; D018046:Protein C Inhibitor / Q000097:blood*; D059748:Proteolysis; D011990:Receptors, Transferrin / Q000097:blood; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods
chemical_list: D000726:Androgen Antagonists; D010455:Peptides; D018046:Protein C Inhibitor; D011990:Receptors, Transferrin