title: Proteomic biomarkers apolipoprotein A1, truncated transthyretin and connective tissue activating protein III enhance the sensitivity of CA125 for detecting early stage epithelial ovarian cancer.
abstract: OBJECTIVE
  The low prevalence of ovarian cancer demands both high sensitivity (>75%) and specificity (99.6%) to achieve a positive predictive value of 10% for successful early detection. Utilizing a two stage strategy where serum marker(s) prompt the performance of transvaginal sonography (TVS) in a limited number (2%) of women could reduce the requisite specificity for serum markers to 98%. We have attempted to improve sensitivity by combining CA125 with proteomic markers.
  
  
  METHODS
  Sera from 41 patients with early stage (I/II) and 51 with late stage (III/IV) epithelial ovarian cancer, 40 with benign disease and 99 healthy individuals, were analyzed to measure 7 proteins [Apolipoprotein A1 (Apo-A1), truncated transthyretin (TT), transferrin, hepcidin, ß-2-microglobulin (ß2M), Connective Tissue Activating Protein III (CTAPIII), and Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4)]. Statistical models were fit by logistic regression, followed by optimization of factors retained in the models determined by optimizing the Akaike Information Criterion. A validation set included 136 stage I ovarian cancers, 140 benign pelvic masses and 174 healthy controls.
  
  
  RESULTS
  In a training set analysis, the 3 most effective biomarkers (Apo-A1, TT and CTAPIII) exhibited 54% sensitivity at 98% specificity, CA125 alone produced 68% sensitivity and the combination increased sensitivity to 88%. In a validation set, the marker panel plus CA125 produced a sensitivity of 84% at 98% specificity (P=0.015, McNemar's test).
  
  
  CONCLUSIONS
  Combining a panel of proteomic markers with CA125 could provide a first step in a sequential two-stage strategy with TVS for early detection of ovarian cancer.
authors.affiliation: U.T. M.D. Anderson Cancer Center, Houston, TX 77030-4009, USA. chclarke@mdanderson.org
authors.forename: Charlotte H
authors.initials: CH
authors.lastname: Clarke
authors.forename: Christine
authors.initials: C
authors.lastname: Yip
authors.forename: Donna
authors.initials: D
authors.lastname: Badgwell
authors.forename: Eric T
authors.initials: ET
authors.lastname: Fung
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Coombes
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.forename: Karen H
authors.initials: KH
authors.lastname: Lu
authors.forename: Robert C
authors.initials: RC
authors.lastname: Bast
mesh_terms: D016632:Apolipoprotein A-I / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood; D000077216:Carcinoma, Ovarian Epithelial; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000097:blood; D008875:Middle Aged; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood* / Q000175:diagnosis / Q000473:pathology; D010051:Ovarian Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000473:pathology; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D011228:Prealbumin / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods
chemical_list: D016632:Apolipoprotein A-I; D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; C451759:MUC16 protein, human; D008565:Membrane Proteins; D010446:Peptide Fragments; D010455:Peptides; D011228:Prealbumin; C009862:connective tissue-activating peptide