title: Discovery of serum biomarkers of ovarian cancer using complementary proteomic profiling strategies.
abstract: OBJECTIVE
  Ovarian cancer is a devastating disease and biomarkers for its early diagnosis are urgently required. Serum may be a valuable source of biomarkers that may be revealed by proteomic profiling. Herein, complementary serum protein profiling strategies were employed for discovery of biomarkers that could discriminate cases of malignant and benign ovarian cancer.
  
  
  METHODS
  Identically collected and processed serum samples from 22 cases of invasive epithelial ovarian cancer, 45 benign ovarian neoplasms, and 64 healthy volunteers were subjected to immunodepletion and protein equalization coupled to 2D-DIGE/MS and multidimensional fractionation coupled to SELDI-TOF profiling with MS/MS for protein identification. Selected candidates were verified by ELISA in samples from malignant (n = 70) and benign (n = 89) cases and combined marker panels tested against serum CA125.
  
  
  RESULTS
  Both profiling platforms were complementary in identifying biomarker candidates, four of which (A1AT, SLPI, APOA4, VDBP) significantly discriminated malignant from benign cases. However, no combination of markers was as good as CA125 for diagnostic accuracy. SLPI was further tested as an early marker using prediagnosis serum samples. While it rose in cases toward diagnosis, it did not discriminate prediagnosis cases from controls.
  
  
  CONCLUSIONS
  The candidate biomarkers warrant further validation in independent sample sets.
authors.affiliation: EGA Institute for Women's Health, University College London, London, UK.
authors.forename: John F
authors.initials: JF
authors.lastname: Timms
authors.forename: Elif
authors.initials: E
authors.lastname: Arslan-Low
authors.forename: Musarat
authors.initials: M
authors.lastname: Kabir
authors.forename: Jenny
authors.initials: J
authors.lastname: Worthington
authors.forename: Stephane
authors.initials: S
authors.lastname: Camuzeaux
authors.forename: John
authors.initials: J
authors.lastname: Sinclair
authors.forename: Joanna
authors.initials: J
authors.lastname: Szaub
authors.forename: Babak
authors.initials: B
authors.lastname: Afrough
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Podust
authors.forename: Evangelia-Ourania
authors.initials: EO
authors.lastname: Fourkala
authors.forename: Myriam
authors.initials: M
authors.lastname: Cubizolles
authors.forename: Florian
authors.initials: F
authors.lastname: Kronenberg
authors.forename: Eric T
authors.initials: ET
authors.lastname: Fung
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Gentry-Maharaj
authors.forename: Usha
authors.initials: U
authors.lastname: Menon
authors.forename: Ian
authors.initials: I
authors.lastname: Jacobs
mesh_terms: D000328:Adult; D000368:Aged; D001054:Apolipoproteins A / Q000097:blood / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000097:blood / Q000175:diagnosis / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000097:blood / Q000378:metabolism; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D001054:Apolipoproteins A; D014408:Biomarkers, Tumor; D001798:Blood Proteins; D020543:Proteome; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; C022205:apolipoprotein A-IV
keywords: Diagnostic biomarkers; MS; Ovarian cancer; Serum profiling