title: Identification of serum amyloid A as a biomarker to distinguish prostate cancer patients with bone lesions.
abstract: BACKGROUND
  Prostate cancer has a propensity to metastasize to the bone. Currently, there are no curative treatments for this stage of the disease. Sensitive biomarkers that can be monitored in the blood to indicate the presence or development of bone metastases and/or response to therapies are lacking. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) is an affinity-based approach that allows sensitive and high-throughput protein profiling and screening of biological samples.
  
  
  METHODS
  We used SELDI-TOF MS for protein profiling of sera from prostate cancer patients (n = 38) with and without bone metastases in our effort to identify individual or multiple serum markers that may be of added benefit to those in current use. Serum was applied to ProteinChip surfaces (H4 and IMAC) to quickly screen samples and detect peaks predominating in the samples obtained from patients with bone metastases. Unique proteins in the bone metastasis cohort observed by SELDI-TOF MS were identified by two-dimensional gel electrophoresis, in-gel trypsin digestion, and tandem MS. The identities of the proteins were confirmed by ELISA and immunodepletion assays.
  
  
  RESULTS
  The cluster of unique proteins in the sera of patients with bone metastases was identified as isoforms of serum amyloid A. Machine-learning algorithms were also used to identify patients with bone metastases with a sensitivity and specificity of 89.5%.
  
  
  CONCLUSIONS
  SELDI-TOF MS protein profiling in combination with other proteomic approaches may provide diagnostic tools with potential clinical applications and serve as tools to aid in the discovery of biomarkers associated with various diseases.
authors.affiliation: British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Lyly
authors.initials: L
authors.lastname: Le
authors.forename: Kim
authors.initials: K
authors.lastname: Chi
authors.forename: Scott
authors.initials: S
authors.lastname: Tyldesley
authors.forename: Stephane
authors.initials: S
authors.lastname: Flibotte
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Diamond
authors.forename: Michael A
authors.initials: MA
authors.lastname: Kuzyk
authors.forename: Marianne D
authors.initials: MD
authors.lastname: Sadar
mesh_terms: D000368:Aged; D000465:Algorithms; D014408:Biomarkers, Tumor / Q000097:blood*; D001859:Bone Neoplasms / Q000175:diagnosis* / Q000556:secondary*; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000473:pathology*; D020033:Protein Isoforms / Q000097:blood; D012680:Sensitivity and Specificity; D000685:Serum Amyloid A Protein / Q000032:analysis*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods
chemical_list: D014408:Biomarkers, Tumor; D015850:Interleukin-6; D020033:Protein Isoforms; D000685:Serum Amyloid A Protein