Levels of circulating cell-free nuclear and mitochondrial DNA in benign and malignant ovarian tumors.
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).


CONCLUSIONS
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.
Zachariah
Rebecca R
RR
Laboratory for Prenatal Medicine and Gynaecologic Oncology, Women's Hospital/Department of Biomedicine, University of Basel, Basel, Switzerland.
Schmid
Seraina
S
Buerki
Nicole
N
Radpour
Ramin
R
Holzgreve
Wolfgang
W
Zhong
Xiaoyan
X
D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood; D002474:Cell-Free System / Q000737:chemistry; D004272:DNA, Mitochondrial / Q000097:blood*; D004273:DNA, Neoplasm / Q000097:blood*; D004715:Endometriosis / Q000097:blood; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000097:blood*; D016133:Polymerase Chain Reaction / Q000379:methods*; D012372:ROC Curve
D014408:Biomarkers, Tumor; D004272:DNA, Mitochondrial; D004273:DNA, Neoplasm