A systematic study on drug-response associated genes using baseline gene expressions of the Cancer Cell Line Encyclopedia.
A systematic study on drug-response associated genes using baseline gene expressions of the Cancer Cell Line Encyclopedia.
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使用癌细胞系百科全书的基线基因表达对药物反应相关基因进行系统研究
DOI：
10.1038/srep22811
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发表时间：
2016-03-10
影响因子：
4.6
通讯作者：
Yang J
中科院分区：
文献类型：
--
作者：
Liu X;Yang J;Zhang Y;Fang Y;Wang F;Wang J;Zheng X;Yang J
我们通过将系统生物学框架应用于癌细胞系百科全书数据来研究药物反应相关（MDR）基因表达。据推测，至少有4,000多个基因被一种药物所抑制，而每种药物的抑制基因数量从几乎0到1226不等。功能富集分析表明，与细胞周期和质膜相关的基因显着富集的cDNA 3基因。此外，在性别之间可能存在两种类型的基因。对于大多数药物而言，男性和女性之间存在显著共享的基因，而对于一些靶向性别特异性癌症的药物而言，很少有基因倾向于在两种性别之间共享（例如，PD-0332991用于乳腺癌和卵巢癌）。我们的分析还显示，年轻和老年样本之间的α-淀粉酶基因存在显著差异，这表明在癌症个体化治疗中考虑年龄效应的必要性。最后，差异模块和关键驱动程序分析确认细胞周期相关模块为药物敏感性的最高差异模块。这些分析还揭示了TSPO、TP 53和许多其他免疫或细胞周期相关基因的作用，这些基因是启动子网络模块的重要关键驱动因素。这些关键驱动因素提供了新的药物靶点，以提高癌症治疗的敏感性。
We have studied drug-response associated (DRA) gene expressions by applying a systems biology framework to the Cancer Cell Line Encyclopedia data. More than 4,000 genes are inferred to be DRA for at least one drug, while the number of DRA genes for each drug varies dramatically from almost 0 to 1,226. Functional enrichment analysis shows that the DRA genes are significantly enriched in genes associated with cell cycle and plasma membrane. Moreover, there might be two patterns of DRA genes between genders. There are significantly shared DRA genes between male and female for most drugs, while very little DRA genes tend to be shared between the two genders for a few drugs targeting sex-specific cancers (e.g., PD-0332991 for breast cancer and ovarian cancer). Our analyses also show substantial difference for DRA genes between young and old samples, suggesting the necessity of considering the age effects for personalized medicine in cancers. Lastly, differential module and key driver analyses confirm cell cycle related modules as top differential ones for drug sensitivity. The analyses also reveal the role ofTSPO,TP53, and many other immune or cell cycle related genes as important key drivers for DRA network modules. These key drivers provide new drug targets to improve the sensitivity of cancer therapy.