Plasma cell-free DNA in ovarian cancer: an independent prognostic biomarker.
BACKGROUND
Cell-free DNA reflects both normal and tumor-derived DNA released into the circulation through cellular necrosis and apoptosis. The authors sought to determine the role of preoperative total plasma cell-free DNA levels in predicting clinical outcome in patients with ovarian cancer.


METHODS
After institutional review board consent, DNA was extracted from plasma of 164 women with invasive epithelial ovarian carcinoma (EOC), 49 with benign ovarian neoplasms, and 75 age-matched controls. The samples were randomly divided into training (n = 144) and validation (n = 144) sets. Quantification of cell-free DNA was performed using real-time polymerase chain reaction for beta-globin, and the number of genome equivalents (GE) per milliliter of plasma was determined. Cell-free DNA was correlated with clinicopathologic parameters.


RESULTS
The training and validation sets were similar in terms of demographic features. In the training set, EOC patients had a median preoperative cell-free DNA level of 10,113 GE/mL, compared with patients with benign ovarian neoplasms (median, 2365 GE/mL; P < .0001) and controls (median, 1912 GE/mL, P < .0001). Cell-free DNA >22,000 GE/mL was significantly associated with decreased patient survival (P < .001). After adjusting for other clinical variables, preoperative cell-free DNA >22,000 GE/mL was an independent predictor (P = .02) for disease-specific survival. Analysis of the validation set confirmed significantly higher cell-free DNA levels in EOC (median, 13,672 GE/mL) and that cell-free DNA >22,000 GE/mL was associated with a 2.83-fold increased risk of death from disease (P < .001).


CONCLUSIONS
Preoperative plasma total cell-free DNA levels are significantly elevated in patients with EOC. Elevated plasma cell-free DNA is an independent predictor for death from disease in ovarian cancer.
Kamat
Aparna A
AA
Department of Gynecologic Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77230, USA.
Baldwin
Mathew
M
Urbauer
Diana
D
Dang
Diana
D
Han
Liz Y
LY
Godwin
Andrew
A
Karlan
Beth Y
BY
Simpson
Joe L
JL
Gershenson
David M
DM
Coleman
Robert L
RL
Bischoff
Farideh Z
FZ
Sood
Anil K
AK
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D002474:Cell-Free System; D004273:DNA, Neoplasm / Q000097:blood*; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000097:blood / Q000235:genetics* / Q000401:mortality; D010949:Plasma / Q000737:chemistry*; D016133:Polymerase Chain Reaction; D057234:Preoperative Period; D011379:Prognosis; D015203:Reproducibility of Results
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm