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Yurkovetsky Z , Skates S , Lomakin A , Nolen B , Pulsipher T , Modugno F , Marks J , Godwin A , Gorelik E , Jacobs I , Menon U , Lu K , Badgwell D , Bast RC , Lokshin AE
Development of a Multimarker Assay for Early Detection of Ovarian Cancer
Journal of Clinical Oncology. 2010 May;28(13) :2159-2166
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Abstract
Purpose Early detection of ovarian cancer has great promise to improve clinical outcome. Patients and 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. Conclusion 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.
Notes
Yurkovetsky, Zoya Skates, Steven Lomakin, Aleksey Nolen, Brian Pulsipher, Trenton Modugno, Francesmary Marks, Jeffrey Godwin, Andrew Gorelik, Elieser Jacobs, Ian Menon, Usha Lu, Karen Badgwell, Donna Bast, Robert C., Jr. Lokshin, Anna E. Amer soc clinical oncology Alexandria 589us