Prediction of in vivo radiation dose status in radiotherapy patients using ex vivo and in vivo gene expression signatures.
Prediction of in vivo radiation dose status in radiotherapy patients using ex vivo and in vivo gene expression signatures.
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DOI：
10.1667/rr2420.1
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发表时间：
2011-03
影响因子：
3.4
通讯作者：
Amundson SA
中科院分区：
文献类型：
--
作者：
Paul S;Barker CA;Turner HC;McLane A;Wolden SL;Amundson SA
在发生大规模核事故或使用简易核装置进行攻击后，需要快速进行生物剂量测定以进行分类。作为解决这一需求的一种可能的手段，我们以前定义了体外照射的人外周血白细胞中的基因表达特征，该特征可以高精度地预测辐射暴露的水平。我们现在使用接受全身照射(TBI)的患者的血液在体内演示这一原理。全基因组微阵列分析已经确定了对外周血液中的体内辐射暴露有显著反应的基因。根据脑外伤患者数据建立的3近邻分类器正确地预测了样本受到0、1.25或3.75Gy射线照射，准确率为94%(P<；0.001)，即使包括来自健康供者对照的样本。使用先前根据体外照射数据定义的签名，以98%的准确率对相同的样品进行分类。样本也可以100%准确地归类为暴露或未暴露。体外照射是一种适当的模型，可以提供体内暴露水平的有意义的预测，并且在不同的疾病状态和独立的样本集上签名是健壮的，这是在应用基因表达进行生物剂量测定方面的重要进展。
After a large-scale nuclear accident or an attack with an improvised nuclear device, rapid biodosimetry would be needed for triage. As a possible means to address this need, we previously defined a gene expression signature in human peripheral white blood cells irradiated ex vivo that predicts the level of radiation exposure with high accuracy. We now demonstrate this principle in vivo using blood from patients receiving total-body irradiation (TBI). Whole genome microarray analysis has identified genes responding significantly to in vivo radiation exposure in peripheral blood. A 3-nearest neighbor classifier built from the TBI patient data correctly predicted samples as exposed to 0, 1.25 or 3.75 Gy with 94% accuracy (P < 0.001) even when samples from healthy donor controls were included. The same samples were classified with 98% accuracy using a signature previously defined from ex vivo irradiation data. The samples could also be classified as exposed or not exposed with 100% accuracy. The demonstration that ex vivo irradiation is an appropriate model that can provide meaningful prediction of in vivo exposure levels, and that the signatures are robust across diverse disease states and independent sample sets, is an important advance in the application of gene expression for biodosimetry.