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

Obstet Gynecol. 2008 Oct;112(4):843-50. doi: 10.1097/AOG.0b013e3181867bc0.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers, Tumor / blood
  • Cell-Free System / chemistry
  • DNA, Mitochondrial / blood*
  • DNA, Neoplasm / blood*
  • Endometriosis / blood
  • Female
  • Humans
  • Ovarian Neoplasms / blood*
  • Polymerase Chain Reaction / methods*
  • ROC Curve

Substances

  • Biomarkers, Tumor
  • DNA, Mitochondrial
  • DNA, Neoplasm