title: Comparison of candidate serologic markers for type I and type II ovarian cancer.
abstract: OBJECTIVE
  To examine the value of individual and combinations of ovarian cancer associated blood biomarkers for the discrimination between plasma of patients with type I or II ovarian cancer and disease-free volunteers.
  
  
  METHODS
  Levels of 14 currently promising ovarian cancer-related biomarkers, including CA125, macrophage inhibitory factor-1 (MIF-1), leptin, prolactin, osteopontin (OPN), insulin-like growth factor-II (IGF-II), autoantibodies (AAbs) to eight proteins: p53, NY-ESO-1, p16, ALPP, CTSD, B23, GRP78, and SSX, were measured in the plasma of 151 ovarian cancer patients, 23 with borderline ovarian tumors, 55 with benign tumors and 75 healthy controls.
  
  
  RESULTS
  When examined individually, seven candidate biomarkers (MIF, Prolactin, CA-125, OPN, Leptin, IGF-II and p53 AAbs) had significantly different plasma levels between type II ovarian cancer patients and healthy controls. Based on the receiver operating characteristic (ROC) curves constructed and area under the curve (AUC) calculated, CA125 exhibited the greatest power to discriminate the plasma samples of type II cancer patients from normal volunteers (AUC 0.9310), followed by IGF-II (AUC 0.8514), OPN (AUC 0.7888), leptin (AUC 0.7571), prolactin (AUC 0.7247), p53 AAbs (AUC 0.7033), and MIF (AUC 0.6992). p53 AAbs levels exhibited the lowest correlation with CA125 levels among the six markers, suggesting the potential of p53 AAbs as a biomarker independent of CA125. Indeed, p53 AAbs increased the AUC of ROC curve to the greatest extent when combining CA125 with one of the other markers. At a fixed specificity of 100%, the addition of p53 AAbs to CA125 increased sensitivity from 73.8% to 85.7% to discriminate type II cancer patients from normal controls. Notably, seropositivity of p53 AAbs is comparable in type II ovarian cancer patients with negative and positive CA125, but has no value for type I ovarian cancer patients.
  
  
  CONCLUSIONS
  p53 AAbs might be a useful blood-based biomarker for the detection of type II ovarian cancer, especially when combined with CA125 levels.
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Lu
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Kuhn
authors.forename: Robert E
authors.initials: RE
authors.lastname: Bristow
authors.forename: Robert L
authors.initials: RL
authors.lastname: Giuntoli
authors.forename: Susanne Krüger
authors.initials: SK
authors.lastname: Kjær
authors.forename: Ie-Ming
authors.initials: IeM
authors.lastname: Shih
authors.forename: Richard B S
authors.initials: RB
authors.lastname: Roden
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood; D000091342:Endoplasmic Reticulum Chaperone BiP; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000097:blood / Q000276:immunology; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000097:blood* / Q000175:diagnosis; D016159:Tumor Suppressor Protein p53 / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D001323:Autoantibodies; D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; C104948:CTAG1B protein, human; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; C451759:MUC16 protein, human; D008565:Membrane Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53