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Plasma cell-free DNA in ovarian cancer: an independent prognostic biomarker Kamat AA; Baldwin M; Urbauer D; Dang D; Han LY; Godwin A; Karlan BY; Simpson JL; Gershenson DM; Coleman RL; Bischoff FZ; Sood AKCancer 2010[Apr]; 116 (8): 1918-25BACKGROUND: 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.|Adult[MESH]|Aged[MESH]|Aged, 80 and over[MESH]|Biomarkers, Tumor/*blood[MESH]|Cell-Free System[MESH]|DNA, Neoplasm/*blood[MESH]|Female[MESH]|Humans[MESH]|Middle Aged[MESH]|Ovarian Neoplasms/blood/*genetics/mortality[MESH]|Plasma/*chemistry[MESH]|Polymerase Chain Reaction[MESH]|Preoperative Period[MESH]|Prognosis[MESH]|Reproducibility of Results[MESH] |
