title: Development of a multimarker assay for early detection of ovarian cancer.
abstract: OBJECTIVE
  Early detection of ovarian cancer has great promise to improve clinical outcome.
  
  
  METHODS
  Ninety-six serum biomarkers were analyzed in sera from healthy women and from patients with ovarian cancer, benign pelvic tumors, and breast, colorectal, and lung cancers, using multiplex xMAP bead-based immunoassays. A Metropolis algorithm with Monte Carlo simulation (MMC) was used for analysis of the data.
  
  
  RESULTS
  A training set, including sera from 139 patients with early-stage ovarian cancer, 149 patients with late-stage ovarian cancer, and 1,102 healthy women, was analyzed with MMC algorithm and cross validation to identify an optimal biomarker panel discriminating early-stage cancer from healthy controls. The four-biomarker panel providing the highest diagnostic power of 86% sensitivity (SN) for early-stage and 93% SN for late-stage ovarian cancer at 98% specificity (SP) was comprised of CA-125, HE4, CEA, and VCAM-1. This model was applied to an independent blinded validation set consisting of sera from 44 patients with early-stage ovarian cancer, 124 patients with late-stage ovarian cancer, and 929 healthy women, providing unbiased estimates of 86% SN for stage I and II and 95% SN for stage III and IV disease at 98% SP. This panel was selective for ovarian cancer showing SN of 33% for benign pelvic disease, SN of 6% for breast cancer, SN of 0% for colorectal cancer, and SN of 36% for lung cancer.
  
  
  CONCLUSIONS
  A panel of CA-125, HE4, CEA, and VCAM-1, after additional validation, could serve as an initial stage in a screening strategy for epithelial ovarian cancer.
authors.affiliation: University of Pittsburgh Hillman Cancer Center, 5117 Centre Ave, Pittsburgh, PA 15213, USA.
authors.forename: Zoya
authors.initials: Z
authors.lastname: Yurkovetsky
authors.forename: Steven
authors.initials: S
authors.lastname: Skates
authors.forename: Aleksey
authors.initials: A
authors.lastname: Lomakin
authors.forename: Brian
authors.initials: B
authors.lastname: Nolen
authors.forename: Trenton
authors.initials: T
authors.lastname: Pulsipher
authors.forename: Francesmary
authors.initials: F
authors.lastname: Modugno
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Marks
authors.forename: Andrew
authors.initials: A
authors.lastname: Godwin
authors.forename: Elieser
authors.initials: E
authors.lastname: Gorelik
authors.forename: Ian
authors.initials: I
authors.lastname: Jacobs
authors.forename: Usha
authors.initials: U
authors.lastname: Menon
authors.forename: Karen
authors.initials: K
authors.lastname: Lu
authors.forename: Donna
authors.initials: D
authors.lastname: Badgwell
authors.forename: Robert C
authors.initials: RC
authors.lastname: Bast
authors.forename: Anna E
authors.initials: AE
authors.lastname: Lokshin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood; D002272:Carcinoembryonic Antigen / Q000097:blood; D003627:Data Interpretation, Statistical; D055088:Early Detection of Cancer; D030501:Epididymal Secretory Proteins / Q000032:analysis; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000706:statistics & numerical data; D008403:Mass Screening / Q000379:methods* / Q000706:statistics & numerical data; D008875:Middle Aged; D009010:Monte Carlo Method; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D023083:beta-Defensins
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D002272:Carcinoembryonic Antigen; C426184:DEFB126 protein, human; D030501:Epididymal Secretory Proteins; D019010:Vascular Cell Adhesion Molecule-1; D023083:beta-Defensins