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

Rebecca R Zachariah, Zachariah RR, Rebecca Zachariah, Seraina Schmid, Schmid S, Nicole Buerki, Ramin Radpour, Holzgreve W, Wolfgang Holzgreve, Xiaoyan Zhong, Zhong X
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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This study evaluated circulating cell-free nuclear and mitochondrial DNA levels in serum and plasma from patients with epithelial ovarian cancer, benign ovarian tumors, endometriosis, and healthy controls using a quantitative multiplex polymerase chain reaction assay. The researchers found that individuals with epithelial ovarian cancer exhibited significantly higher amounts of both nuclear and mitochondrial DNA compared to healthy controls and those with benign ovarian diseases. While the analysis revealed a significant difference in mitochondrial DNA levels between the cancer group and the endometriosis group, no such distinction was observed for nuclear DNA, and neither biomarker correlated with pathological parameters or CA-125 measurements in cancer patients. Relevance to endometriosis: The paper includes an endometriosis cohort as a comparative control group to distinguish malignant from benign conditions, specifically noting differences in mitochondrial DNA levels between ovarian cancer and endometriosis patients.

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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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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. LEVEL OF EVIDENCE: III

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Condition tags

endometriosis

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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