Circulating free DNA as biomarker and source for mutation detection in metastatic colorectal cancer.
Circulating free DNA as biomarker and source for mutation detection in metastatic colorectal cancer.
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将游离DNA作为生物标志物和转移性结直肠癌突变的来源。
DOI：
10.1371/journal.pone.0108247
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Jakobsen A
中科院分区：
文献类型：
--
作者：
Spindler KL;Pallisgaard N;Andersen RF;Brandslund I;Jakobsen A
血浆中循环的无细胞DNA（cfDNA）已显示出作为各种癌症生物标志物的潜力，并可能成为肿瘤突变检测的重要来源。我们研究的目的是在健康个体的队列中建立cfDNA的正常范围，并将其与转移性结直肠癌（mCRC）患者的四个队列进行比较。我们还研究了cfDNA的预后价值，并分析了血浆中的肿瘤特异性KRAS突变。该研究是一项前瞻性生物标志物评估，在四个连续的II期试验，包括229例化疗难治性mCRC患者和100名健康个体。从EDTA血液样品获得血浆，并使用如前所述的内部ARMS-qPCR评估DNA等位基因和KRAS突变等位基因的总数。与对照相比，mCRC中的中值cfDNA水平更高（p <0.0001）。ROC分析显示AUC为0.9486（p<0.00001）。数据显示，当通过cfDNA的四分位数将患者分类以及基于对照组的正常范围上限将患者分类为低cfDNA组或高cfDNA组时，随着基线cfDNA水平的增加，OS受损（中位OS分别为10.2（8.3-11.7）和5.2（4.6-5.9）个月，HR 1.78，p = 0.0006）。多变量分析证实了cfDNA的独立预后价值（cfDNA四分位数每次增加，HR 1.5（95%CI 1.3-1.7））。血浆和组织中KRAS突变的总体一致性较高（85%）。这些数据证实了血浆中cfDNA测量的预后价值和用所提出的方法进行突变检测的实用性。
Circulating cell-free DNA (cfDNA) in plasma has shown potential as biomarker in various cancers and could become an importance source for tumour mutation detection. The objectives of our study were to establish a normal range of cfDNA in a cohort of healthy individuals and to compare this with four cohorts of metastatic colorectal cancer (mCRC) patients. We also investigated the prognostic value of cfDNA and analysed the tumour-specific KRAS mutations in the plasma. The study was a prospective biomarker evaluation in four consecutive Phase II trials, including 229 patients with chemotherapy refractory mCRC and 100 healthy individuals. Plasma was obtained from an EDTA blood-sample, and the total number of DNA alleles and KRAS mutated alleles were assessed using an in-house ARMS-qPCR as previously described. Median cfDNA levels were higher in mCRC compared to controls (p <0.0001). ROC analysis revealed an AUC of 0.9486 (p<0.00001). Data showed impaired OS with increasing levels of baseline cfDNA both when categorising patients by quartiles of cfDNA and into low or high cfDNA groups based on the upper normal range of the control group (Median OS 10.2 (8.3–11.7) and 5.2 (4.6–5.9) months, respectively, HR 1.78, p = 0.0006). Multivariate analysis confirmed an independent prognostic value of cfDNA (HR 1.5 (95% CI 1.3–1.7) for each increase in the cfDNA quartile). The overall concordance of KRAS mutations in plasma and tissue was high (85%). These data confirm the prognostic value of cfDNA measurement in plasma and utility for mutation detection with the method presented.
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影响因子：
50.5
作者：
Spindler, K. -L. Garm;Pallisgaard, N.;Jakobsen, A.
通讯作者：
Jakobsen, A.
影响因子：
8.4
作者：
Qiu, Li-Xin;Mao, Chen;Chen, Qing
通讯作者：
Chen, Qing
DOI：
10.1073/pnas.0507904102
发表时间：
2005-11-08
影响因子：
11.1
作者：
Diehl, F;Li, M;Vogelstein, B
通讯作者：
Vogelstein, B
影响因子：
64.8
作者：
Misale, Sandra;Yaeger, Rona;Hobor, Sebastijan;Scala, Elisa;Janakiraman, Manickam;Liska, David;Valtorta, Emanuele;Schiavo, Roberta;Buscarino, Michela;Siravegna, Giulia;Bencardino, Katia;Cercek, Andrea;Chen, Chin-Tung;Veronese, Silvio;Zanon, Carlo;Sartore-Bianchi, Andrea;Gambacorta, Marcello;Gallicchio, Margherita;Vakiani, Efsevia;Boscaro, Valentina;Medico, Enzo;Weiser, Martin;Siena, Salvatore;Di Nicolantonio, Federica;Solit, David;Bardelli, Alberto
通讯作者：
Bardelli, Alberto
影响因子：
11.5
作者：
Spindler, Karen-Lise Garm;Pallisgaard, Niels;Jakobsen, Anders
通讯作者：
Jakobsen, Anders