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 (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.

• Authors: Irene Visintin, Ziding Feng, Gary Longton, David C Ward, Ayesha B Alvero, Yinglei Lai, Jeannette Tenthorey, Aliza Leiser, Ruben Flores-Saaib, Herbert Yu, Masoud Azori, Thomas Rutherford, Peter E Schwartz, Gil Mor
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 14 Issue 4 Pg. 1065-72 (Feb 15 2008) ISSN: 1078-0432 [Print] United States
• PMID: 18258665 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• CA-125 Antigen
• Cytokines
• GDF15 protein, human
• Growth Differentiation Factor 15
• IGF2 protein, human
• Leptin
• Osteopontin
• Insulin-Like Growth Factor II
• Prolactin

Topics

• Adult
• Aged
• Aged, 80 and over
• Area Under Curve
• Biomarkers, Tumor (blood)
• CA-125 Antigen (blood)
• Cytokines (blood)
• Early Diagnosis
• Enzyme-Linked Immunosorbent Assay
• False Positive Reactions
• Female
• Growth Differentiation Factor 15
• Humans
• Insulin-Like Growth Factor II (analysis)
• Leptin (blood)
• Middle Aged
• Osteopontin (blood)
• Ovarian Neoplasms (blood, diagnosis)
• Prolactin (blood)
• Sensitivity and Specificity