Research on circadian clock genes in common abdominal malignant tumors

Chronobiol Int. 2019 Jul;36(7):906-918. doi: 10.1080/07420528.2018.1477792. Epub 2019 Apr 24.

Abstract

Circadian rhythm describes the 24-h oscillation in physiology and behavior of living organisms and presents a timing controller for life activity. Studies in recent years have reported that the abnormal expression of clock genes is closely related to the development of common abdominal malignant tumors. The expression of the 14 kinds of clock genes in 6 abdominal malignant tumors from Cancer Genome Atlas (TCGA) data was integrated and analyzed using R and Perl programming languages to show the association between clock gene expression and prognosis of cancer patients. Analysis of TCGA data indicated that the overexpression of Per1-3, Cry2, CLOCK, NR1D2 and RORA with underexpression of Timeless and NPAS2 was associated with a favorable prognosis in kidney cancer. In liver cancer, high expressions of Cry2 and RORA were correlated with prolonged overall survival (OS) in patients, while high expressions of NPAS2 and Timeless were correlated with a poor survival. High expression of CLOCK was positively correlated with OS in colon cancer patients. High expression of Cry2 and low expression of DEC1 were associated with a favorable prognosis in pancreatic cancer patients, respectively. Most of these clock-genes expressions were closely related to the clinical stage and degree of tumor differentiation of patients. Aberrant clock gene expression is related to the biological characteristics of abdominal malignant tumors, which likely has a causal role in cancer development and survival.

Keywords: Circadian clock; abdominal malignant tumor; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abdominal Neoplasms / genetics*
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Cell Cycle Proteins / genetics
  • Circadian Clocks / genetics*
  • Circadian Rhythm / genetics*
  • Cryptochromes / genetics
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Genome, Human
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Male
  • Nerve Tissue Proteins / genetics
  • Nuclear Receptor Subfamily 1, Group F, Member 1 / genetics
  • Oscillometry
  • Period Circadian Proteins / genetics
  • Prognosis

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • CRY2 protein, human
  • Cell Cycle Proteins
  • Cryptochromes
  • Intracellular Signaling Peptides and Proteins
  • NPAS2 protein, human
  • Nerve Tissue Proteins
  • Nuclear Receptor Subfamily 1, Group F, Member 1
  • PER3 protein, human
  • Period Circadian Proteins
  • RORA protein, human
  • TIMELESS protein, human