Research Paper Volume 12, Issue 14 pp 14620—14632

Circadian clock is associated with tumor microenvironment in kidney renal clear cell carcinoma

Liangcheng Zhou1, *, , Zhili Luo2, *, , Zuwei li3, *, , Qinying Huang4, ,

  • 1 Department of Nephrology, Maoming People’s Hospital, Maoming 525000, China
  • 2 Department of Rehabilitative Medicine, Gaozhou People’s Hospital, Maoming 525200, China
  • 3 Department of Urology, Gaozhou People’s Hospital, Maoming 525200, China
  • 4 Department of Ophthalmology, Shantou University Medical College, Shantou 515041, China
* Equal contribution

Received: March 12, 2020       Accepted: June 4, 2020       Published: July 18, 2020
How to Cite

Copyright: © 2020 Zhou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Background: Kidney renal clear cell carcinoma (KIRC) is one of the most prevalent malignancies with high incidence and mortality. The circadian clock, which is also involved in the regulation of the immune system and tumor microenvironment, is an internal timing system that allows organisms to adjust biological processes and behaviors according to geophysical time.

Result: A wide range of circadian clock genes are epigenetically altered in KIRC, and associated with the overall survival and disease-free survival of patients. SNV analysis revealed missense mutation and splice site to be the most common variant types of circadian clock genes in KIRC. Several circadian clock genes were involved in the regulation of some cancer-related hallmark pathways, including apoptosis and cell cycle pathway. Further, immune infiltrates analysis not only revealed that the expression of circadian clock genes is associated with immune cell infiltrates, but also that somatic copy-number alteration of circadian clock genes could inhibit the immune infiltrates. Moreover, enrichment analysis implied that the circadian clock genes could regulate transcription factor activity and circadian rhythm in KIRC.

Conclusion: Our results demonstrate the potential of chrono-immunotherapy as a candidate option for the management of KIRC.

Method: Multi-omics analysis was performed to comprehensively determine the roles of core circadian clock genes in KIRC.


KIRC: Clear cell renal cell carcinoma; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; BP: Biological processes; CC: Cellular components; MF: Molecular functions; PPI: Protein-protein interaction; SNV: Single Nucleotide Variation.