title: Early detection of ovarian cancer in samples pre-diagnosis using CA125 and MALDI-MS peaks.
abstract: OBJECTIVE
  A nested case-control discovery study was undertaken to test whether information within the serum peptidome can improve on the utility of CA125 for early ovarian cancer detection.
  
  
  METHODS
  High-throughput matrix-assisted laser desorption ionisation mass spectrometry (MALDI-MS) was used to profile 295 serum samples from women pre-dating their ovarian cancer diagnosis and from 585 matched control samples. Classification rules incorporating CA125 and MS peak intensities were tested for discriminating ability.
  
  
  RESULTS
  Two peaks were found which in combination with CA125 discriminated cases from controls up to 15 and 11 months before diagnosis, respectively, and earlier than using CA125 alone. One peak was identified as connective tissue-activating peptide III (CTAPIII), whilst the other was putatively identified as platelet factor 4 (PF4). ELISA data supported the down-regulation of PF4 in early cancer cases.
  
  
  CONCLUSIONS
  Serum peptide information with CA125 improves lead time for early detection of ovarian cancer. The candidate markers are platelet-derived chemokines, suggesting a link between platelet function and tumour development.
authors.affiliation: Cancer Proteomics Laboratory, EGA Institute for Women's Health, University College London, Cruciform Building 1.1.03, Gower Street, London, WC1E 6BT, UK. jtimms@wibr.ucl.ac.uk
authors.forename: John F
authors.initials: JF
authors.lastname: Timms
authors.forename: Usha
authors.initials: U
authors.lastname: Menon
authors.forename: Dmitry
authors.initials: D
authors.lastname: Devetyarov
authors.forename: Ali
authors.initials: A
authors.lastname: Tiss
authors.forename: Stephane
authors.initials: S
authors.lastname: Camuzeaux
authors.forename: Katherine
authors.initials: K
authors.lastname: McCurrie
authors.forename: Ilia
authors.initials: I
authors.lastname: Nouretdinov
authors.forename: Brian
authors.initials: B
authors.lastname: Burford
authors.forename: Celia
authors.initials: C
authors.lastname: Smith
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Gentry-Maharaj
authors.forename: Rachel
authors.initials: R
authors.lastname: Hallett
authors.forename: Jeremy
authors.initials: J
authors.lastname: Ford
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Luo
authors.forename: Volodya
authors.initials: V
authors.lastname: Vovk
authors.forename: Alex
authors.initials: A
authors.lastname: Gammerman
authors.forename: Rainer
authors.initials: R
authors.lastname: Cramer
authors.forename: Ian
authors.initials: I
authors.lastname: Jacobs
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood*; D016022:Case-Control Studies; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000097:blood*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000175:diagnosis*; D010455:Peptides; D010978:Platelet Factor 4 / Q000097:blood*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; C451759:MUC16 protein, human; D008565:Membrane Proteins; D010455:Peptides; D010978:Platelet Factor 4; C009862:connective tissue-activating peptide