Clin Cancer Res. 2008 Feb 15;14(4):1065-72.
Diagnostic markers for early detection of
ovarian cancer.
Visintin I, Feng Z, Longton G, Ward DC, Alvero
AB, Lai Y, Tenthorey J, Leiser A, Flores-Saaib
R, Yu H, Azori M, Rutherford T, Schwartz PE, Mor
G.
Department of Obstetrics and Gynecology, Yale
University School of Medicine, New Haven,
Connecticut 06520, USA.
Purpose:
Early detection would significantly
decrease the mortality rate of ovarian cancer.
In this study, we characterize and validate the
combination of six serum biomarkers that
discriminate between disease-free and ovarian
cancer patients with high efficiency.
EXPERIMENTAL
Design:
We analyzed 362 healthy
controls and 156 newly diagnosed ovarian cancer
patients. Concentrations of leptin, prolactin,
osteopontin, insulin-like growth factor II,
macrophage inhibitory factor, and CA-125 were
determined using a multiplex, bead-based,
immunoassay system. All six markers were
evaluated in a training set (181 samples from
the control group and 113 samples from OC
patients) and a test set (181 sample control
group and 43 ovarian cancer).
Results:
Multiplex
and ELISA exhibited the same pattern of
expression for all the biomarkers. None of the
biomarkers by themselves were good enough to
differentiate healthy versus cancer cells.
However, the combination of the six markers
provided a better differentiation than CA-125.
Four models with <2% classification error in
training sets all had significant improvement
(sensitivity 84%-98% at specificity 95%) over
CA-125 (sensitivity 72% at specificity 95%) in
the test set. The chosen model correctly
classified 221 out of 224 specimens in the test
set, with a classification accuracy of 98.7%.
Conclusions:
We describe the first blood
biomarker test with a sensitivity of 95.3% and a
specificity of 99.4% for the detection of
ovarian cancer. Six markers provided a
significant improvement over CA-125 alone for
ovarian cancer detection. Validation was
performed with a blinded cohort. This novel
multiplex platform has the potential for
efficient screening in patients who are at high
risk for ovarian cancer.
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