Gene expression changes in peripheral blood cells provide insight into the biological mechanisms associated with regimen-related toxicities in patients being treated for head and neck cancers
Gene expression changes in peripheral blood cells provide insight into the biological mechanisms associated with regimen-related toxicities in patients being treated for head and neck cancers
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DOI：
10.1016/j.oraloncology.2006.03.014
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发表时间：
2007-03-01
期刊：
影响因子：
4.8
通讯作者：
Ramoni, M.
中科院分区：
文献类型：
--
作者：
Sonis, S.;Haddad, R.;Ramoni, M.
接受放射治疗的患者容易出现一系列局部和全身毒性，包括粘膜炎、口干、疲劳和厌食症。最近才认识到毒性发展背后的生物学复杂性和相似性。粘膜屏障损伤是研究得最好的一个”，基于动物组织样本的基因表达模式增加了对它的理解。虽然基于组织样本的基因表达调查是有价值的，但它的使用排除了相对于常见致病机制的更普遍的结论。此外，试图通过顺序采样来定义基因表达变化的动力学是不切实际的。我们的目标是：1；确定在接受放化疗的患者中使用PBM是否可以检测到毒性发展过程中基因表达的变化；2. 利用图论和通路分析表征表达基因之间的关系；和3。评估特定基因表达、典型途径和功能网络之间的潜在关系，以解释方案相关毒性的发病机制。设计：对5例出现方案相关毒性的头颈癌患者进行了微阵列分析，使用放化疗开始前和开始放化疗2周后获得的pbm衍生的cRNA。我们创建了一个2周内新表达基因的数据库，并通过典型途径分析、围绕焦点基因的区域网络编译和个体功能网络全球化模型的开发，评估了它们相对于毒性的潜在意义。已知的毒性致病机制与我们的数据开发的基因、途径和网络之间有很强的一致性。对毒性发展中未被怀疑的基因进行了投票。我们的研究结果支持了辐射诱导毒性具有共同潜在机制的概念，并证明了PBM作为遗传研究的RNA来源的实用性。该方法可广泛应用于方案相关毒性的研究。(c) 2006 Elsevier Ltd.版权所有。
Patients treated with radiotherapy are prone to a constellation of local and systemic toxicities including mucositis, xerostomia, fatigue and anorexia. The biological complexities and similarities underlying the development of toxicities have recently been realized. Mucosal barrier injury is one of the best studied" and gene expression patterns, based on animal tissue samples, have added to its understanding. While investigations gene expression based on tissue samples was valuable, its use precludes more generalizable conclusions relative to common pathogenic mechanisms., Additionally, attempting to define the kinetics of changes in gene expression by sequential sampling is pragmatically unrealistic. Our objectives were: 1. to determine if changes in gene expression could be detected during toxicity development using PBM from patients receiving chemoradiation; 2. to characterize the relationship of expressed genes using graph theory and pathway analysis; and 3. to evaluate potential relationships between the expression of particular genes, canonical pathways, and functional networks in explaining the pathogenesis of regimen-related toxicities. DESIGN: Microarray analysis was performed using PBM-derived cRNA obtained before and 2 weeks after the initiation of chemoradiation in five patients with head and neck cancer who developed documented regimen-related toxicities. We created a database of those genes newly expressed at 2 weeks and evaluated their potential significance relative to toxicity, by canonical pathway analysis, compilation of regional networks around focus genes, and development of a model globalizing the individual functional networks. There was strong concordance between known pathogenic mechanisms of toxicity and the genes, pathways, and networks developed by our data. A rote was elicited for unsuspected genes in toxicity development. Our results support the concept that radiation induced toxicities have common underlying mechanisms and demonstrate the utility of PBM as an RNA source for genetic studies. This methodology could be broadly applicable to the study of regimen-related toxicities. (c) 2006 Elsevier Ltd. All rights reserved.