The Genomic Landscape and Pharmacogenomic Interactions of Clock Genes in Cancer Chronotherapy. - PubMed - NCBI
Cell Syst. 2018 Mar 1. pii: S2405-4712(18)30050-4. doi: 10.1016/j.cels.2018.01.013. [Epub ahead of print]
The Genomic Landscape and Pharmacogenomic Interactions of Clock Genes in Cancer Chronotherapy.
Ye Y1,
Xiang Y1,
Ozguc FM1,
Kim Y1,
Liu CJ2,
Park PK3,
Hu Q3,
Diao L4,
Lou Y5,
Lin C6,
Guo AY7,
Zhou B8,
Wang L8,
Chen Z1,
Takahashi JS9,
Mills GB10,
Yoo SH11,
Han L12.
Abstract
Cancer chronotherapy, treatment at specific times during circadian rhythms, endeavors to optimize anti-tumor effects and to 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 The Cancer Genome Atlas, Cancer Therapeutics Response Portal, and The Genomics of Drug Sensitivity in Cancer 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 chromatin immunoprecipitation sequencing 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. KEYWORDS:
cancer; chronotherapy; circadian rhythms; clinical actionable genes; clock genes; drug; pharmacogenomics
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