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

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 oscillat...

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Autores principales: Chai, Ruihuan, Liao, Min, Ou, Ling, Tang, Qian, Liang, Youfang, Li, Nan, Huang, Wei, Wang, Xiao, Zheng, Kai, Wang, Shaoxiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9273445/
https://www.ncbi.nlm.nih.gov/pubmed/35832846
http://dx.doi.org/10.1155/2022/9774879
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author Chai, Ruihuan
Liao, Min
Ou, Ling
Tang, Qian
Liang, Youfang
Li, Nan
Huang, Wei
Wang, Xiao
Zheng, Kai
Wang, Shaoxiang
author_facet Chai, Ruihuan
Liao, Min
Ou, Ling
Tang, Qian
Liang, Youfang
Li, Nan
Huang, Wei
Wang, Xiao
Zheng, Kai
Wang, Shaoxiang
author_sort Chai, Ruihuan
collection PubMed
description 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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spelling pubmed-92734452022-07-12 Circadian Clock Genes Act as Diagnostic and Prognostic Biomarkers of Glioma: Clinic Implications for Chronotherapy Chai, Ruihuan Liao, Min Ou, Ling Tang, Qian Liang, Youfang Li, Nan Huang, Wei Wang, Xiao Zheng, Kai Wang, Shaoxiang Biomed Res Int Research Article 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. Hindawi 2022-07-04 /pmc/articles/PMC9273445/ /pubmed/35832846 http://dx.doi.org/10.1155/2022/9774879 Text en Copyright © 2022 Ruihuan Chai et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Chai, Ruihuan
Liao, Min
Ou, Ling
Tang, Qian
Liang, Youfang
Li, Nan
Huang, Wei
Wang, Xiao
Zheng, Kai
Wang, Shaoxiang
Circadian Clock Genes Act as Diagnostic and Prognostic Biomarkers of Glioma: Clinic Implications for Chronotherapy
title Circadian Clock Genes Act as Diagnostic and Prognostic Biomarkers of Glioma: Clinic Implications for Chronotherapy
title_full Circadian Clock Genes Act as Diagnostic and Prognostic Biomarkers of Glioma: Clinic Implications for Chronotherapy
title_fullStr Circadian Clock Genes Act as Diagnostic and Prognostic Biomarkers of Glioma: Clinic Implications for Chronotherapy
title_full_unstemmed Circadian Clock Genes Act as Diagnostic and Prognostic Biomarkers of Glioma: Clinic Implications for Chronotherapy
title_short Circadian Clock Genes Act as Diagnostic and Prognostic Biomarkers of Glioma: Clinic Implications for Chronotherapy
title_sort circadian clock genes act as diagnostic and prognostic biomarkers of glioma: clinic implications for chronotherapy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9273445/
https://www.ncbi.nlm.nih.gov/pubmed/35832846
http://dx.doi.org/10.1155/2022/9774879
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