Dysregulation of Circadian Clock Genes as Significant Clinic Factor in the Tumorigenesis of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the leading cause of cancer-related mortality worldwide due to its asymptomatic onset and poor survival rate. This highlights the urgent need for developing novel diagnostic markers for early HCC detection. The circadian clock is important for maintaining cellular h...

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Autores principales:	Youfang Liang, Shaoxiang Wang, Xin Huang, Ruihuan Chai, Qian Tang, Rong Yang, Xiaoqing Huang, Xiao Wang, Kai Zheng
Formato:	article
Lenguaje:	EN
Publicado:	Hindawi Limited 2021
Materias:	Computer applications to medicine. Medical informatics R858-859.7
Acceso en línea:	https://doaj.org/article/034a2bc31188404a8bfd6bd8016fe4ec
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spelling	oai:doaj.org-article:034a2bc31188404a8bfd6bd8016fe4ec2021-11-08T02:36:35ZDysregulation of Circadian Clock Genes as Significant Clinic Factor in the Tumorigenesis of Hepatocellular Carcinoma1748-671810.1155/2021/8238833https://doaj.org/article/034a2bc31188404a8bfd6bd8016fe4ec2021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/8238833https://doaj.org/toc/1748-6718Hepatocellular carcinoma (HCC) is the leading cause of cancer-related mortality worldwide due to its asymptomatic onset and poor survival rate. This highlights the urgent need for developing novel diagnostic markers for early HCC detection. The circadian clock is important for maintaining cellular homeostasis and is tightly associated with key tumorigenesis-associated molecular events, suggesting the so-called chronotherapy. An analysis of these core circadian genes may lead to the discovery of biological markers signaling the onset of the disease. In this study, the possible functions of 13 core circadian clock genes (CCGs) in HCC were systematically analyzed with the aim of identifying ideal biomarkers and therapeutic targets. Profiles of HCC patients with clinical and gene expression data were downloaded from The Cancer Genome Atlas and International Cancer Genome Consortium. Various bioinformatics methods were used to investigate the roles of circadian clock genes in HCC tumorigenesis. We found that patients with high TIMELESS expression or low CRY2, PER1, and RORA expressions have poor survival. Besides, a prediction model consisting of these four CCGs, the tumor-node-metastasis (TNM) stage, and sex was constructed, demonstrating higher predictive accuracy than the traditional TNM-based model. In addition, pathway analysis showed that these four CCGs are involved in the cell cycle, PI3K/AKT pathway, and fatty acid metabolism. Furthermore, the network of these four CCGs-related coexpressed genes and immune infiltration was analyzed, which revealed the close association with B cells and nTreg cells. Notably, TIMELESS exhibited contrasting effects against CRY2, PER1, and RORA in most situations. In sum, our works revealed that these circadian clock genes TIMELESS, CRY2, PER1, and RORA can serve as potential diagnostic and prognostic biomarkers, as well as therapeutic targets, for HCC patients, which may promote HCC chronotherapy by rhythmically regulating drug sensitivity and key cellular signaling pathways.Youfang LiangShaoxiang WangXin HuangRuihuan ChaiQian TangRong YangXiaoqing HuangXiao WangKai ZhengHindawi LimitedarticleComputer applications to medicine. Medical informaticsR858-859.7ENComputational and Mathematical Methods in Medicine, Vol 2021 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Computer applications to medicine. Medical informatics R858-859.7
spellingShingle	Computer applications to medicine. Medical informatics R858-859.7 Youfang Liang Shaoxiang Wang Xin Huang Ruihuan Chai Qian Tang Rong Yang Xiaoqing Huang Xiao Wang Kai Zheng Dysregulation of Circadian Clock Genes as Significant Clinic Factor in the Tumorigenesis of Hepatocellular Carcinoma
description	Hepatocellular carcinoma (HCC) is the leading cause of cancer-related mortality worldwide due to its asymptomatic onset and poor survival rate. This highlights the urgent need for developing novel diagnostic markers for early HCC detection. The circadian clock is important for maintaining cellular homeostasis and is tightly associated with key tumorigenesis-associated molecular events, suggesting the so-called chronotherapy. An analysis of these core circadian genes may lead to the discovery of biological markers signaling the onset of the disease. In this study, the possible functions of 13 core circadian clock genes (CCGs) in HCC were systematically analyzed with the aim of identifying ideal biomarkers and therapeutic targets. Profiles of HCC patients with clinical and gene expression data were downloaded from The Cancer Genome Atlas and International Cancer Genome Consortium. Various bioinformatics methods were used to investigate the roles of circadian clock genes in HCC tumorigenesis. We found that patients with high TIMELESS expression or low CRY2, PER1, and RORA expressions have poor survival. Besides, a prediction model consisting of these four CCGs, the tumor-node-metastasis (TNM) stage, and sex was constructed, demonstrating higher predictive accuracy than the traditional TNM-based model. In addition, pathway analysis showed that these four CCGs are involved in the cell cycle, PI3K/AKT pathway, and fatty acid metabolism. Furthermore, the network of these four CCGs-related coexpressed genes and immune infiltration was analyzed, which revealed the close association with B cells and nTreg cells. Notably, TIMELESS exhibited contrasting effects against CRY2, PER1, and RORA in most situations. In sum, our works revealed that these circadian clock genes TIMELESS, CRY2, PER1, and RORA can serve as potential diagnostic and prognostic biomarkers, as well as therapeutic targets, for HCC patients, which may promote HCC chronotherapy by rhythmically regulating drug sensitivity and key cellular signaling pathways.
format	article
author	Youfang Liang Shaoxiang Wang Xin Huang Ruihuan Chai Qian Tang Rong Yang Xiaoqing Huang Xiao Wang Kai Zheng
author_facet	Youfang Liang Shaoxiang Wang Xin Huang Ruihuan Chai Qian Tang Rong Yang Xiaoqing Huang Xiao Wang Kai Zheng
author_sort	Youfang Liang
title	Dysregulation of Circadian Clock Genes as Significant Clinic Factor in the Tumorigenesis of Hepatocellular Carcinoma
title_short	Dysregulation of Circadian Clock Genes as Significant Clinic Factor in the Tumorigenesis of Hepatocellular Carcinoma
title_full	Dysregulation of Circadian Clock Genes as Significant Clinic Factor in the Tumorigenesis of Hepatocellular Carcinoma
title_fullStr	Dysregulation of Circadian Clock Genes as Significant Clinic Factor in the Tumorigenesis of Hepatocellular Carcinoma
title_full_unstemmed	Dysregulation of Circadian Clock Genes as Significant Clinic Factor in the Tumorigenesis of Hepatocellular Carcinoma
title_sort	dysregulation of circadian clock genes as significant clinic factor in the tumorigenesis of hepatocellular carcinoma
publisher	Hindawi Limited
publishDate	2021
url	https://doaj.org/article/034a2bc31188404a8bfd6bd8016fe4ec
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_version_	1718443064094097408

Dysregulation of Circadian Clock Genes as Significant Clinic Factor in the Tumorigenesis of Hepatocellular Carcinoma

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