Levels of Circulating Cell-Free Nuclear and Mitochondrial DNA in Benign and Malignant Ovarian Tumors

Rebecca Zachariah, Rebecca R Zachariah, Seraina Schmid, Nicole Buerki, Ramin Radpour, Wolfgang Holzgreve, Xiaoyan Zhong
Obstetrics and gynecology · 2008 · vol. 112(4) , pp. 843–850 · doi:10.1097/aog.0b013e3181867bc0 · PMID:18827127 · W2076316408
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Patients with epithelial ovarian cancer showed significantly higher plasma levels of circulating cell-free nuclear and mitochondrial DNA compared to healthy controls and those with benign ovarian diseases.

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Abstract

OBJECTIVE: To analyze the levels of circulating cell-free nuclear DNA and circulating cell-free mitochondrial DNA in patients with benign and malignant ovarian tumors using a gold-standard assay and to investigate whether quantitative alterations of the circulating cell-free species have values in the management of the patients. METHODS: One hundred four patients were recruited for this study. We developed a quantitative, multiplex polymerase chain reaction to measure the levels of circulating cell-free nuclear DNA and circulating cell-free mitochondrial DNA in serum and plasma of patients with epithelial ovarian cancer, benign epithelial ovarian tumors, or endometriosis. The levels of the circulating cell-free DNA were compared with those of a healthy, age-matched control group. RESULTS: The patients with epithelial ovarian cancer had significantly higher amounts of circulating cell-free nuclear DNA and circulating cell-free mitochondrial DNA in plasma compared with the healthy control group (mean of nuclear DNA 10,723/2,591 and mean of mitochondrial DNA 4,918,978/2,294,264, P=.009 and 0.022, respectively) and with the other group with benign ovarian diseases (mean of nuclear DNA 10,723/2,965 and mean of mitochondrial DNA 4,918,978/1,597,551, P=.027 and 0.002, respectively). However, no relationship between levels of the circulating cell-free DNA and the pathological parameters as well as CA 125 measurement in patients with epithelial ovarian cancer was found. A significant difference between the epithelial ovarian cancer and endometriosis group was found in circulating cell-free mitochondrial DNA but not in circulating cell-free nuclear DNA (mean of mitochondrial DNA 4,918,978/2,273,988 and mean of nuclear DNA 10,723/3,291, P=.013 and 0.105, respectively). CONCLUSION: Elevated levels of circulating cell-free nuclear DNA and circulating cell-free mitochondrial DNA in epithelial ovarian cancer may have diagnostic value. Our finding suggests that the circulating molecules might be potential biomarkers in the disease.

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Condition tags

mesh:D004715endometriosis

MeSH descriptors

DNA, Mitochondrial DNA, Neoplasm Ovarian Neoplasms Polymerase Chain Reaction Adult Biomarkers, Tumor Biomarkers, Tumor Cell-Free System Cell-Free System DNA, Mitochondrial DNA, Neoplasm Endometriosis Endometriosis Female Humans Ovarian Neoplasms Polymerase Chain Reaction ROC Curve

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