Radiation-induced gene expression in human subcutaneous fibroblasts is predictive of radiation-induced fibrosis
Radiation-induced gene expression in human subcutaneous fibroblasts is predictive of radiation-induced fibrosis
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DOI：
10.1016/j.radonc.2007.09.013
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发表时间：
2008-03-01
影响因子：
5.7
通讯作者：
Overgaard, Jens
中科院分区：
文献类型：
--
作者：
Rodningen, Aug Kristin;Borresen-Dale, Anne-Lise;Overgaard, Jens
背景和目的：乳腺癌患者在接受电离辐射（IR）治疗后，正常组织的反应存在很大差异。电离放射治疗最常见的长期不良反应之一是放射性纤维化（RIF），在过去几年中，已经进行了几次尝试来开发RIF的预测分析。我们的目的是确定乳腺癌患者成纤维细胞的基础和辐射诱导的转录谱，这些转录谱可能与这些患者中RIF的个体风险有关。（从低到高风险分为五类）采用两种不同的方案进行辐照：1 x 3.5戈伊，在照射后2和24 h分离RNA，以及3 x 3.5戈伊，间隔24 h的分次方案，在最后一次给药后2 h分离RNA。还从未处理的成纤维细胞中分离RNA。基础和辐射诱导的基因表达谱的转录差异进行了研究，使用15 K cDNA微阵列，SAM和PAM分析结果。结果：60差异表达的基因被确定应用SAM对10例RIF的最高风险和4例RIF的最低风险后的分割方案。这些基因与细胞凋亡、细胞外基质重塑/细胞粘附、增殖和ROS清除等过程中的已知功能相关。最小的一组18个基因被确定，可以区分高风险从低风险的患者后的fractionated scheme.Conclusions：分类的18个基因可能提供的基础上，放疗后的正常组织反应的预测分析，并提供新的见解RIF的分子机制。(c)2007爱思唯尔爱尔兰有限公司保留所有权利。
Background and purpose: Breast cancer patients show a large variation in normal tissue reactions after ionizing radiation (IR) therapy. One of the most common long-term adverse effects of ionizing radiotherapy is radiation-induced fibrosis (RIF), and several attempts have been made over the last years to develop predictive assays for RIF. Our aim was to identify basal and radiation-induced transcriptional profiles in fibroblasts from breast cancer patients that might be related to the individual risk of RIF in these patients.Materials and methods: Fibroblast cell lines from 31 individuals with variable risk of RIF (grouped into five classes from low to high risk) were irradiated with two different schemes: 1 x 3.5 Gy with RNA isolated 2 and 24 h after irradiation, and a fractionated scheme with 3 x 3.5 Gy in intervals of 24 h with RNA isolated 2 h after the last dose. RNA was also isolated from non-treated fibroblasts. Transcriptional differences in basal and radiation-induced gene expression profiles were investigated using 15K cDNA microarrays, and results analyzed by both SAM and PAM.Results: Sixty differentially expressed genes were identified by applying SAM on 10 patients with the highest risk of RIF and the four patients with the lowest risk of RIF after the fractionated scheme. The genes were associated with known functions in processes like apoptosis, extracellular matrix remodelling/cell adhesion, proliferation and ROS scavenging. A minimum set of 18 genes were identified that could differentiate high risk from low risk-patients after the fractionated scheme.Conclusions: The classifier of 18 genes may provide basis for a predictive assay for normal tissue reactions after radiotherapy, and provide new insight into the molecular mechanisms of RIF. (c) 2007 Elsevier Ireland Ltd. All rights reserved.