Circadian clock associates with tumor microenvironment in thoracic cancers

Aging (Albany NY). 2019 Dec 23;11(24):11814-11828. doi: 10.18632/aging.102450. Epub 2019 Dec 23.

Abstract

The application of cancer chronotherapy is to treat cancers based on at specific times during circadian rhythms. Previous studies have characterized the impact of circadian clock on tumorigenesis and specific immune cells. Here, by using multi-omics computation techniques, we systematically characterized the distinct roles of core circadian clock genes in thoracic cancers including lung adenocarcinoma, lung squamous cell carcinoma, and esophageal carcinoma. Strikingly, a wide range of core clock genes are epigenetically altered in lung adenocarcinomas and lung squamous cell carcinomas but not esophageal carcinomas. Further cancer hallmark analysis reveals that several core clock genes highly correlate with apoptosis and cell cycle such as RORA and PER2. Interestingly, our results reveal that CD4 and CD8 T cells are correlated with core clock molecules especially in lung adenocarcinomas and lung squamous cell carcinomas, indicating that chrono-immunotherapy may serve as a candidate option for future cancer management.

Keywords: circadian clock; immune cells; immunotherapy; multi-omics; tumor microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Circadian Clocks / genetics*
  • DNA Methylation
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / immunology
  • Esophageal Neoplasms / pathology
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / immunology
  • Lung Neoplasms / pathology
  • Transcriptome / genetics
  • Tumor Microenvironment / physiology*