The Genomic Landscape and Pharmacogenomic Interactions of Clock Genes in Cancer Chronotherapy

Youqiong Ye, Yu Xiang, Fatma Muge Ozguc, Yoonjin Kim, Chun Jie Liu, Peter K. Park, Qingsong Hu, Lixia Diao, Yanyan Lou, Chunru Lin, An Yuan Guo, Bingying Zhou, Li Wang, Zheng Chen, Joseph S. Takahashi, Gordon Mills, Seung Hee Yoo, Leng Han

Research output: Contribution to journalArticle

29 Scopus citations

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. 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.

Original languageEnglish (US)
JournalCell Systems
DOIs
StateAccepted/In press - Jan 1 2018
Externally publishedYes

Keywords

  • Cancer
  • Chronotherapy
  • Circadian rhythms
  • Clinical actionable genes
  • Clock genes
  • Drug
  • Pharmacogenomics

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

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    Ye, Y., Xiang, Y., Ozguc, F. M., Kim, Y., Liu, C. J., Park, P. K., Hu, Q., Diao, L., Lou, Y., Lin, C., Guo, A. Y., Zhou, B., Wang, L., Chen, Z., Takahashi, J. S., Mills, G., Yoo, S. H., & Han, L. (Accepted/In press). The Genomic Landscape and Pharmacogenomic Interactions of Clock Genes in Cancer Chronotherapy. Cell Systems. https://doi.org/10.1016/j.cels.2018.01.013