Department of Gynecologic Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77230, USA.
Cancer. 2010 Apr 15;116(8):1918-25. doi: 10.1002/cncr.24997.
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.
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.
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).
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.
游离细胞 DNA 反映了通过细胞坏死和凋亡释放到循环中的正常和肿瘤源性 DNA。作者试图确定术前总血浆游离 DNA 水平在预测卵巢癌患者临床结局中的作用。
在机构审查委员会同意后，从 164 名浸润性上皮性卵巢癌（EOC）女性、49 名良性卵巢肿瘤患者和 75 名年龄匹配的对照者的血浆中提取 DNA。这些样本被随机分为训练（n=144）和验证（n=144）组。使用实时聚合酶链反应检测β-球蛋白定量，确定每毫升血浆中的基因组当量（GE）数。游离 DNA 与临床病理参数相关。
训练组和验证组在人口统计学特征方面相似。在训练组中，EOC 患者术前游离 DNA 中位数为 10113 GE/ml，明显高于良性卵巢肿瘤患者（中位数，2365 GE/ml；P<0.0001）和对照组（中位数，1912 GE/ml，P<0.0001）。游离 DNA>22000 GE/ml 与患者生存时间缩短显著相关（P<0.001）。在校正其他临床变量后，术前游离 DNA>22000 GE/ml 是疾病特异性生存的独立预测因子（P=0.02）。对验证组的分析进一步证实 EOC 患者的游离 DNA 水平明显更高（中位数，13672 GE/ml），游离 DNA>22000 GE/ml 与疾病死亡风险增加 2.83 倍相关（P<0.001）。
EOC 患者术前血浆总游离 DNA 水平显著升高。血浆游离 DNA 升高是卵巢癌疾病死亡的独立预测因子。
