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.
Sood, Anil K.
中科院分区:
医学1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.

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细胞游离DNA(CFDNA)反映了通过细胞坏死和凋亡释放到循环中的正常和肿瘤来源的DNA。我们试图确定术前总血浆CFDNA水平在预测卵巢癌患者临床结局中的作用。在IRB同意后,从164名患有浸润性上皮性卵巢癌(EOC)的女性、49名患有良性卵巢肿瘤的女性和75名年龄匹配的对照者的血浆中提取DNA。样本被随机分为训练集(n=144)和验证集(n=144)。使用β-珠蛋白的实时PCR进行CFDNA的定量,并测定每ml血浆的基因组当量(GE)数。CFDNA与临床病理参数相关。训练集和验证集在人口统计学特征方面相似。在训练集中,EOC患者术前CFDNA水平的中位数为10,113 GE/ml,与良性卵巢肿瘤患者(中位数为2,365 GE/ml; p<0.0001)和对照组(中位数为1,912 GE/ml,p<0.0001)相比。CFDNA >22,000 GE/ml与患者存活率降低显著相关(p<0.001)。在调整其他临床变量后,术前CFDNA > 22,000 GE/ml是疾病特异性生存的独立预测因子(p=0.02)。对验证集的分析证实了EOC中CFDNA水平显著较高(中位数为13,672 GE/ml),CFDNA > 22,000 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CFDNA水平显著升高。血浆CFDNA水平升高是卵巢癌死亡的独立预测因子。
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.
DOI: 10.1200/jco.1996.14.11.2968
发表时间: 1996-11-01
影响因子: 45.3
作者:
Ahmed, FY;Wiltshaw, E;Gore, ME
通讯作者: Gore, ME
DOI: 10.1002/cncr.11496
发表时间: 2003-07-15
期刊: CANCER
影响因子: 6.2
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发表时间: 2002-07-01
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DOI: 10.1038/nm0996-1035
发表时间: 1996-09-01
期刊: NATURE MEDICINE
影响因子: 82.9
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通讯作者: Sidransky, D
DOI: 10.1046/j.1537-2995.2001.41020276.x
发表时间: 2001-02-01
期刊: TRANSFUSION
影响因子: 2.9
作者:
Lee, TH;Montalvo, L;Busch, MP
通讯作者: Busch, MP