Related Experiment Video

Updated: Jan 28, 2026

Monitoring Cell-autonomous Circadian Clock Rhythms of Gene Expression Using Luciferase Bioluminescence Reporters
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Monitoring Cell-autonomous Circadian Clock Rhythms of Gene Expression Using Luciferase Bioluminescence Reporters

Published on: September 27, 2012

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Dysregulation, functional implications, and prognostic ability of the circadian clock across cancers

Zekun Liu1,2, Kai Yu2, Jian Zheng2

  • 1Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Cancer Medicine
|February 22, 2019
PubMed

Insights

Cancer

Area of Science:

  • Oncology
  • Molecular Biology
  • Chronobiology

Background:

  • Circadian rhythm's role in tumor suppression is debated, with some evidence suggesting disruption has anticancer effects.
  • Understanding circadian clock gene aberrations in cancer is crucial for developing novel therapeutic strategies.

Purpose of the Study:

  • To systematically analyze circadian clock gene aberrances across various cancers using TCGA data.
  • To establish a circadian clock index (CCI) and evaluate its relationship with cancer characteristics and patient survival.

Main Methods:

  • Analysis of mutations, copy number alterations, and DNA methylation of core clock genes (PER1/2/3, CLOCK, CRY1/2, ARNTL) in TCGA cancer data.
  • Principal component analysis to establish the circadian clock index (CCI).
  • Enrichment analysis of signaling pathways and correlation studies with immunophenoscores, immunophenotypes, and survival data.

Main Results:

  • Core clock genes showed low mutation/copy number alteration frequencies but were frequently downregulated by DNA methylation across cancers.
  • The circadian clock index (CCI) was significantly lower in HBV-associated hepatocellular carcinoma.
  • High CCI values correlated with enriched MAPK, JAK-STAT, and immune-related pathways, as well as favorable immunophenotypes and improved patient survival.

Conclusions:

  • Circadian clock genes exhibit widespread downregulation via DNA methylation in cancer, with a notable decrease in HBV-associated hepatocellular carcinoma.
  • The CCI serves as a valuable indicator of overall clock gene expression, correlating with immune infiltration and better survival outcomes.
  • These findings offer insights into cancer's molecular mechanisms and potential therapeutic targets related to circadian rhythm regulation.
Keywords:
cancer biologygenomicsimmunologysurvival

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