Plasma cell-free DNA in ovarian cancer: an independent prognostic biomarker.
Plasma cell-free DNA in ovarian cancer: an independent prognostic biomarker.
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DOI:
10.1002/cncr.24997
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发表时间:
2010-04-15
期刊:
影响因子:
6.2
通讯作者:
Sood, Anil K.
中科院分区:
文献类型:
--
作者:
Kamat, Aparna A.;Baldwin, Mathew;Urbauer, Diana;Dang, Diana;Han, Liz Y.;Godwin, Andrew;Karlan, Beth Y.;Simpson, Joe L.;Gershenson, David M.;Coleman, Robert L.;Bischoff, Farideh Z.;Sood, Anil K.
Cell-free DNA (CFDNA) reflects both normal and tumor-derived DNA released into the circulation through cellular necrosis and apoptosis. We sought to determine the role of pre-operative total plasma CFDNA levels in predicting clinical outcome in patients with ovarian cancer. Following IRB 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 CFDNA was performed using real-time PCR for beta-globin and the number of genome equivalents (GE) per ml of plasma was determined. CFDNA was correlated with clinicopathologic parameters. The training and validation sets were similar in terms of demographic features. In the training set, EOC patients had a median pre-operative CFDNA level of 10,113 GE/ml, compared to patients with benign ovarian neoplasms (median 2,365 GE/ml; p<0.0001) and controls (median 1,912 GE/ml, p<0.0001). CFDNA >22,000GE/ml was significantly associated with decreased patient survival (p<0.001). After adjusting for other clinical variables, pre-operative CFDNA > 22,000 GE/ml was an independent predictor (p=0.02) for disease-specific survival. Analysis of the validation set confirmed significantly higher CFDNA levels in EOC (median 13,672 GE/ml) and that CFDNA >22,000 GE/ml was associated with a 2.83-fold increased risk of death from disease (p<0.001). Pre-operative plasma total CFDNA levels are significantly elevated in patients with EOC. Elevated plasma CFDNA is an independent predictor for death from disease in ovarian cancer.
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