Investigation of radiosensitivity gene signatures in cancer cell lines.

Investigation of radiosensitivity gene signatures in cancer cell lines.
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DOI:
10.1371/journal.pone.0086329
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
West CM
West CM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hall JS;Iype R;Senra J;Taylor J;Armenoult L;Oguejiofor K;Li Y;Stratford I;Stern PL;O'Connor MJ;Miller CJ;West CM

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内在放射敏感性是放射治疗反应的重要因素,但在人类肿瘤中没有常规评估方法。目前正在推导基因签名,并且一些先前通过NCI-60细胞系组的表达谱分析生成。假设专注于更同质的肿瘤类型将是一种更好的方法。使用两个细胞系群组,其来源于宫颈癌[n = 16]和头颈癌[n = 11]。    放射敏感性以2戈伊(SF 2)照射后的存活分数(survival fraction)为指标。使用</>Affyssin基因芯片外显子1.0ST(宫颈)或U133 A Plus 2(头颈部)阵列研究放射敏感性和放射抗性细胞系(SF 2中位数)之间的差异基因表达。分层上皮标志物p63的表达反映了与起源组织相关的细胞系队列内存在差异。在138个被鉴定为与SF 2相关的基因中,只有2个(1.4%)在宫颈癌细胞系和头颈癌细胞系(MGST 1和TFPI)之间是一致的,并且这些基因没有划分基于SF 2的已发表的NCI-60细胞系。将三种已发表的放射敏感性特征应用于我们的队列中,取得了不同的成功。最初在NCI-60细胞系上训练的一个基因签名在所有三个细胞系数据集中确实部分分离了敏感和抗性细胞系。这些发现并没有证实我们的假设,但表明一个共同的转录签名可以反映肿瘤的放射敏感性的异质性起源。
Intrinsic radiosensitivity is an important factor underlying radiotherapy response, but there is no method for its routine assessment in human tumours. Gene signatures are currently being derived and some were previously generated by expression profiling the NCI-60 cell line panel. It was hypothesised that focusing on more homogeneous tumour types would be a better approach. Two cell line cohorts were used derived from cervix [n = 16] and head and neck [n = 11] cancers. Radiosensitivity was measured as surviving fraction following irradiation with 2 Gy (SF2) by clonogenic assay. Differential gene expression between radiosensitive and radioresistant cell lines (SF2</> median) was investigated using Affymetrix GeneChip Exon 1.0ST (cervix) or U133A Plus2 (head and neck) arrays. There were differences within cell line cohorts relating to tissue of origin reflected by expression of the stratified epithelial marker p63. Of 138 genes identified as being associated with SF2, only 2 (1.4%) were congruent between the cervix and head and neck carcinoma cell lines (MGST1 and TFPI), and these did not partition the published NCI-60 cell lines based on SF2. There was variable success in applying three published radiosensitivity signatures to our cohorts. One gene signature, originally trained on the NCI-60 cell lines, did partially separate sensitive and resistant cell lines in all three cell line datasets. The findings do not confirm our hypothesis but suggest that a common transcriptional signature can reflect the radiosensitivity of tumours of heterogeneous origins.
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