Plasma cell‐free DNA in ovarian cancer: An independent prognostic biomarker

Abstract

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 β‐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. Cancer 2010. © 2010 American Cancer Society.