The Genomic Landscape and Pharmacogenomic Interactions of Clock Genes in Cancer Chronotherapy.
The Genomic Landscape and Pharmacogenomic Interactions of Clock Genes in Cancer Chronotherapy.
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DOI：
10.1016/j.cels.2018.01.013
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发表时间：
2018-03-28
期刊：
影响因子：
9.3
通讯作者：
Han L
中科院分区：
文献类型：
--
作者：
Ye Y;Xiang Y;Ozguc FM;Kim Y;Liu CJ;Park PK;Hu Q;Diao L;Lou Y;Lin C;Guo AY;Zhou B;Wang L;Chen Z;Takahashi JS;Mills GB;Yoo SH;Han L
癌症时间疗法，即在昼夜节律的特定时间进行治疗，致力于优化抗肿瘤效果并降低毒性。然而，缺乏时钟基因的全面表征及其在癌症中的临床相关性。我们通过分析 TCGA、CTRP 和 GDSC 数据库的数据，系统地描述了 32 种癌症类型中时钟基因的变化。时钟基因的表达改变与多种癌症类型的关键致癌途径、患者生存、肿瘤分期和亚型相关。与正常组织相比，时钟基因和基因组中其他基因的表达之间的相关性在癌组织中发生了改变。我们通过分析共表达、蛋白质-蛋白质相互作用和 ChIP-seq 数据确定了时钟基因与临床可操作基因之间的相互作用，并发现时钟基因表达与癌细胞系中的抗癌药物敏感性相关。我们的研究对不同癌症类型的生物钟进行了全面分析，并强调了癌症时间疗法的潜在临床效用。 Ye等人全面分析了多种人类癌症中时钟基因和昼夜节律的变化，揭示了时钟基因与临床可操作基因之间的强烈相互作用，这凸显了昼夜节律在癌症时间治疗中的临床实用性。
Cancer chronotherapy, treatment at specific times during circadian rhythms, endeavors to optimize anti-tumor effects and lower toxicity. However, comprehensive characterization of clock genes and their clinical relevance in cancer is lacking. We systematically characterized the alterations of clock genes across 32 cancer types by analyzing data from TCGA, CTRP, and GDSC databases. Expression alterations of clock genes are associated with key oncogenic pathways, patient survival, tumor stage and subtype in multiple cancer types. Correlations between expression of clock genes and of other genes in the genome were altered in cancerous versus normal tissues. We identified interactions between clock genes and clinically actionable genes by analyzing co-expression, protein-protein interaction and ChIP-seq data, and also found that clock gene expression is correlated to anti-cancer drug sensitivity in cancer cell lines. Our study provides a comprehensive analysis of the circadian clock across different cancer types and highlights potential clinical utility of cancer chronotherapy. Ye et al comprehensively analyzed alterations of clock genes and circadian rhythms across multiple human cancers, and revealed strong interactions between clock genes and clinically actionable genes, which highlights the clinical utility of circadian timing in cancer chronotherapy.
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影响因子：
16.6
作者：
Amabile, Giovanni;Di Ruscio, Annalisa;Mueller, Fabian;Welner, Robert S.;Yang, Henry;Ebralidze, Alexander K.;Zhang, Hong;Levantini, Elena;Qi, Lihua;Martinelli, Giovanni;Brummelkamp, Thijn;Le Beau, Michelle M.;Figueroa, Maria E.;Bock, Christoph;Tenen, Daniel G.
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关于癌症基因组地图集的泛伴奏蛋白质组学观点。
影响因子：
16.6
作者：
Akbani, Rehan;Ng, Patrick Kwok Shing;Werner, Henrica M. J.;Shahmoradgoli, Maria;Zhang, Fan;Ju, Zhenlin;Liu, Wenbin;Yang, Ji-Yeon;Yoshihara, Kosuke;Li, Jun;Ling, Shiyun;Seviour, Elena G.;Ram, Prahlad T.;Minna, John D.;Diao, Lixia;Tong, Pan;Heymach, John V.;Hill, Steven M.;Dondelinger, Frank;Stadler, Nicolas;Byers, Lauren A.;Meric-Bernstam, Funda;Weinstein, John N.;Broom, Bradley M.;Verhaak, Roeland G. W.;Liang, Han;Mukherjee, Sach;Lu, Yiling;Mills, Gordon B.
通讯作者：
Mills, Gordon B.
影响因子：
6.4
作者：
Innominato, Pasquale F.;Giacchetti, Sylvie;Levi, Francis A.
通讯作者：
Levi, Francis A.
影响因子：
16
作者：
Heinz S;Benner C;Spann N;Bertolino E;Lin YC;Laslo P;Cheng JX;Murre C;Singh H;Glass CK
通讯作者：
Glass CK