The aberrant expression of rhythm genes affects the genome instability and regulates the cancer immunity in pan-cancer

Cancer Med. 2020 Mar;9(5):1818-1829. doi: 10.1002/cam4.2834. Epub 2020 Jan 12.

Abstract

Although emerging studies showed that certain rhythm genes regulate cancer progression, the expression and roles of the vast majority of rhythm genes in human cancer are largely unknown, and the hallmarks of cancer regulated by rhythm genes have not been detected. In this study, we detected the expression changes of rhythm genes in pan-cancer and found that almost all rhythm genes mutated in all cancer types, and their expression level was significantly altered partially due to abnormal methylation, and several rhythm genes regulate the expression of other rhythm genes in various cancer types. Furthermore, we revealed that rhythm genes are significantly enriched in genome instability and the expression of certain rhythm genes is correlated with the tumor mutation burden, microsatellite instability, and the expression of DNA damage repair genes in most of the detected cancer types. Moreover, rhythm genes are associated with the infiltration of immune cells and the efficiency of immune blockade therapy. This study provides a comprehensive understanding of the roles of rhythm genes in cancer immunity, which may provide a novel method for the diagnosis and treatment of cancer.

Keywords: cancer immunity; circadian rhythm genes; genome instability; microsatellite instability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Circadian Rhythm Signaling Peptides and Proteins / genetics*
  • Computational Biology
  • DNA Damage / immunology
  • DNA Methylation
  • DNA Repair / immunology
  • Datasets as Topic
  • Drug Resistance, Neoplasm / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / immunology*
  • Genomic Instability / immunology*
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology
  • Immune Checkpoint Inhibitors / therapeutic use
  • Microsatellite Instability
  • Neoplasm Invasiveness / genetics
  • Neoplasms / drug therapy
  • Neoplasms / genetics
  • Neoplasms / immunology*
  • Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • Circadian Rhythm Signaling Peptides and Proteins
  • Immune Checkpoint Inhibitors