Research Paper Volume 13, Issue 12 pp 16637—16655
The circadian clock is associated with prognosis and immune infiltration in stomach adenocarcinoma
- 1 Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330000, China
- 2 Department of Emergency, The Second Affiliated Hospital of Nanchang University, Nanchang 330000, China
Received: March 19, 2021 Accepted: June 4, 2021 Published: June 23, 2021https://doi.org/10.18632/aging.203184
How to Cite
Copyright: © 2021 Huang 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: Stomach adenocarcinoma (STAD) is one of the most prevalent malignances and ranks fifth in incidence and third in cancer-related death among all malignances. The prognosis of STAD is poor. The circadian clock is regulated by interlocked transcriptional-translational feedback loops that orchestrate circadian rhythms in some biological processes, including the immune response and metabolism. However, the association between core circadian clock genes and STAD patient prognosis is unclear.
Materials and Methods: In our study, bioinformatics methods were performed to explore the expression and prognostic value of core circadian clock genes in STAD and their association with immune infiltration.
Results: The mRNA levels of CLOCK, CRY1 and NR1D1 were upregulated, while the mRNA levels of CRY2, PER1, PER3 and RORA were downregulated in STAD tissues compared with normal tissues. Core circadian clock genes exert promoting or inhibiting effects on certain cancer-related hallmark pathways, including the DNA damage response, cell cycle, apoptosis and RAS/MAPK pathways. Moreover, core circadian clock genes were linked to drug sensitivity or drug resistance. Prognosis analysis revealed that high expression of PER1 and NR1D1 was associated with poor overall survival, progression-free survival, and disease-free survival rates in STAD patients. Validation analysis further confirmed our result. Immune infiltration analysis demonstrated that the expression of ICOSLG and CD70 was significantly correlated with immune cells, immune biomarkers, chemokines and their receptors.
Conclusions: Our results suggest that NR1D1 and PER1 are prognostic biomarkers and are associated with immune infiltration in STAD.