Diagnostic Markers for Early Detection of Ovarian Cancer

Abstract

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 (181sample 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 221out 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.

ATAD2 is Highly Expressed in Ovarian Carcinomas and Indicates Poor Prognosis

“…However as an individual marker on a single occasion, CA-125 is not sufficiently sensitive and specify to detect most cases of ovarian cancer (Gadducci et al, 2004;Nossov et al, 2008). With appropriate statistical models, combinations of several markers such as leptin, prolactin, osteopon-tin, insulin-like growth factor II (IGF-II), macrophage inhibitory factor (MIF) and CA-125 have become more effective and accurate means for the detection of ovarian tumorgenesis (Visintin et al, 2008;Li et al, 2009;Sorensen et al, 2011), while no reliable method can be used to distinguish tumor stages. ATAD2 is one of the 76 genes identified for prediction of distant metastasis of ER-positive, lymph node-negative, primary breast cancer, which was later validated in a multicenter study (Wang et al, 2005;Foekens et al, 2006;Desmedt et al, 2007;Haibe-Kains et al, 2008).…”

Simple Plex™: A Novel Multi‐Analyte, Automated Microfluidic Immunoassay Platform for the Detection of Human and Mouse Cytokines and Chemokines

“…Quantitative measurement of several proteins in bodily fluids or cellular preparations is critical for the evaluation of biomarker candidates or the study of complex cellular processes, such as inflammation, cancer, and autoimmune diseases 1, 2, 3. Immunoassays are the most common quantitative approach used and have been extensively characterized in terms of sensitivity, reproducibility, and variability 4, 5.…”

Discovery of serum biomarkers of ovarian cancer using complementary proteomic profiling strategies

“…Consequently, biomarkers with improved accuracy for detecting and diagnosing ovarian cancer are urgently required. While several marker panels and algorithms have been reported for differential diagnosis 3, 4, 5, 6, 7, 8, 9, 10, 11, there is as yet insufficient evidence to support their wider clinical use, particularly for…”