Circadian Clock Genes Act as Diagnostic and Prognostic Biomarkers of Glioma: Clinic Implications for Chronotherapy

Chai，Ruihuan1; Liao，Min1; Ou，Ling2,3; Tang，Qian4; Liang，Youfang1; Li，Nan1; Huang，Wei2,3; Wang，Xiao5; Zheng，Kai1; Wang，Shaoxiang1

2022-07-04

10.1155/2022/9774879

Biomed Research International   Impact Factor & Quartile

2314-6133

2314-6141

Gliomas are the most common primary intracranial tumors and closely related to circadian clock. Due to the high mortality and morbidity of gliomas, exploring novel diagnostic and early prognostic markers is necessary. Circadian clock genes (CCGs) play important roles in regulating the daily oscillation of biological processes and the development of tumor. Therefore, we explored the influences that the oscillations of circadian clock genes (CCGs) on diagnosis and prognosis of gliomas using bioinformatics. In this work, we systematically analyzed the rhythmic expression of CCGs in brain and found that some CCGs had strong rhythmic expression; the expression levels were significantly different between day and night. Four CCGs (ARNTL, NPAS2, CRY2, and DBP) with rhythmic expression were not only identified as differentially expressed genes but also had significant independent prognostic ability in the overall survival of glioma patients and were highly correlated with glioma prognosis in COX analysis. Besides, we found that CCG-based predictive model demonstrated higher predictive accuracy than that of the traditional grade-based model; this new prediction model can greatly improve the accuracy of glioma prognosis. Importantly, based on the four CCGs' circadian oscillations, we revealed that patients sampled at night had higher predictive ability. This may help detect glioma as early as possible, leading to early cancer intervention. In addition, we explored the mechanism of CCGs affecting the prognosis of glioma. CCGs regulated the cell cycle, DNA damage, Wnt, mTOR, and MAPK signaling pathways. In addition, it also affects prognosis through gene coexpression and immune infiltration. Importantly, ARNTL can rhythmically modulated the cellular sensitivity to clinic drugs, temozolomide. The optimal point of temozolomide administration should be when ARNTL expression is highest, that is, the effect is better at night. In summary, our study provided a basis for optimizing clinical dosing regimens and chronotherapy for glioma. The four key CCGs can serve as potential diagnostic and prognostic biomarkers for glioma patients, and ARNTL also has obvious advantages in the direction of glioma chronotherapy.

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National Natural Science Foundation of China[82073937] ; Shenzhen Science and Technology Project["GJHZ20200731095200003","JCYJ20180228175059744","JCYJ20210324093602007"] ; Shenzhen Key Medical Discipline Construction Fund[SZXK059] ; SZU Medical Young Scientists Program[71201-000001]

Biotechnology & Applied Microbiology ; Research & Experimental Medicine

Biotechnology & Applied Microbiology ; Medicine, Research & Experimental

WOS:000831612600004

HINDAWI LTD

2-s2.0-85133994100

Web of Science

1.School of Pharmaceutical Sciences,Shenzhen University Health Science Center,Shenzhen,518000,China
2.Bacteriology & Antibacterial Resistance Surveillance Laboratory,Shenzhen Institute of Respiratory Diseases,Shenzhen People's Hospital (The Second Clinical Medical College,Jinan University,Shenzhen,518020,China
3.First Affiliated Hospital,Southern University of Science and Technology,Shenzhen,518020,China
4.School of Pharmacy,Jinan University,Guangzhou,510630,China
5.Department of Pharmacy,Shenzhen People's Hospital (The Second Clinical Medical College,Jinan University,Shenzhen,518020,China

Chai，Ruihuan,Liao，Min,Ou，Ling,et al. Circadian Clock Genes Act as Diagnostic and Prognostic Biomarkers of Glioma: Clinic Implications for Chronotherapy[J]. Biomed Research International,2022,2022.

Chai，Ruihuan.,Liao，Min.,Ou，Ling.,Tang，Qian.,Liang，Youfang.,...&Wang，Shaoxiang.(2022).Circadian Clock Genes Act as Diagnostic and Prognostic Biomarkers of Glioma: Clinic Implications for Chronotherapy.Biomed Research International,2022.

Chai，Ruihuan,et al."Circadian Clock Genes Act as Diagnostic and Prognostic Biomarkers of Glioma: Clinic Implications for Chronotherapy".Biomed Research International 2022(2022).