Development of a multimarker assay for early detection of ovarian cancer.
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.
Yurkovetsky
Zoya
Z
University of Pittsburgh Hillman Cancer Center, 5117 Centre Ave, Pittsburgh, PA 15213, USA.
Skates
Steven
S
Lomakin
Aleksey
A
Nolen
Brian
B
Pulsipher
Trenton
T
Modugno
Francesmary
F
Marks
Jeffrey
J
Godwin
Andrew
A
Gorelik
Elieser
E
Jacobs
Ian
I
Menon
Usha
U
Lu
Karen
K
Badgwell
Donna
D
Bast
Robert C
RC
Lokshin
Anna E
AE
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
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