Identification of a radiation sensitivity gene expression profile in primary fibroblasts derived from patients who developed radiotherapy-induced fibrosis
Identification of a radiation sensitivity gene expression profile in primary fibroblasts derived from patients who developed radiotherapy-induced fibrosis
复制标题
DOI：
10.1016/j.radonc.2014.03.007
复制
发表时间：
2014-05-01
影响因子：
5.7
通讯作者：
Sprung, Carl N.
中科院分区：
文献类型：
--
作者：
Forrester, Helen B.;Li, Jason;Sprung, Carl N.
背景与目的：在放射治疗过程中，正常组织不可避免地暴露在辐射下，导致一小部分患者出现严重的正常组织反应。由于在放射治疗前不能确定敏感人群，因此剂量限制在所有患者，以避免不可接受的严重不良正常组织反应。这一限制限制了对辐射耐受性较强的个体的最佳治疗。遗传变异是个体间正常组织放射敏感性差异的可能来源。因此，在基因组水平上了解放射反应可能为制定个体化治疗和改善放射治疗结果提供知识。材料和方法：利用外显子阵列来比较来自6名患有和不患有严重纤维化的癌症患者的细胞系之间的基本表达谱。这些数据得到了qRT-PCR和RNA-Seq技术的支持。结果：一组基因（FBN2、FST、GPRC5B、NOTCH3、PLCB1、DPT、DDIT4L和SGCG）被确定为辐射诱导纤维化的潜在预测因子。这些基因中有许多与TGF β或视黄酸相关，两者都与纤维化有关。结论：组合基因表达方法为预测放疗前癌症患者的纤维化提供了一种有希望的策略。2014爱思唯尔爱尔兰有限公司版权所有。
Background and purpose: During radiotherapy, normal tissue is unavoidably exposed to radiation which results in severe normal tissue reactions in a small fraction of patients. Because those who are sensitive cannot be determined prior to radiotherapy, the doses are limited to all patients to avoid an unacceptable number of severe adverse normal tissue responses. This limitation restricts the optimal treatment for individuals who are more tolerant to radiation. Genetic variation is a likely source for the normal tissue radiosensitivity variation observed between individuals. Therefore, understanding the radiation response at the genomic level may provide knowledge to develop individualized treatment and improve radiotherapy outcomes.Material and methods: Exon arrays were utilized to compare the basal expression profile between cell lines derived from six cancer patients with and without severe fibrosis. These data were supported by qRT-PCR and RNA-Seq techniques.Results: A set of genes (FBN2, FST, GPRC5B, NOTCH3, PLCB1, DPT, DDIT4L and SGCG) were identified as potential predictors for radiation-induced fibrosis. Many of these genes are associated with TGF beta or retinoic acid both having known links to fibrosis.Conclusion: A combinatorial gene expression approach provides a promising strategy to predict fibrosis in cancer patients prior to radiotherapy. (C) 2014 Elsevier Ireland Ltd. All rights reserved.