机构:[1]Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China华中科技大学同济医学院附属协和医院[2]Sun Yat‐sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China[3]The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China广东省中医院[4]Big Data Research Center, School of Computer Science and Engineering, University of Electronic Science and Technology of China, Chengdu, China
It has been proposed that the circadian rhythm generally plays important roles in tumor suppression, but there is also evidence that disruption of the canonical circadian pathway has anticancer effects. In this study, we systematically analyzed the aberrances of circadian clock genes across cancers based on data from The Cancer Genome Atlas (TCGA). These data showed that the frequencies of mutations and copy number alterations in core clock genes (PER1/2/3, CLOCK, CRY1/2, and ARNTL) were low, but that the expression levels of core clock genes were downregulated by the higher levels of DNA methylation in most tumors. The circadian clock index (CCI) was established through a principal component analysis, and this measure well represents the overall expression of the core clock genes. In fact, the CCI was significantly lower in hepatocellular carcinoma with HBV infection than in other cancers. Furthermore, pathways such as the MAPK, JAK-STAT, and immune-related signaling pathways were enriched in tumors with high CCI values. Interestingly, the CCI was generally positively related to the immunophenoscores and immunophenotypes of tumors. Additionally, the expression levels of core clock genes and the CCI were also generally positively related to survival across cancers. Taken together, the results of this study provide a comprehensive analysis of circadian clock aberrances in cancer, and the results should aid further investigations of the molecular mechanisms of cancer and the development of therapeutic strategies.
基金:
National Natural Science Foundation of China [31501069, 81602461, 81772586, 81772614, 81802438, 81874231, 81502439, U1611261]; Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities [17ykzd32]; China Postdoctoral Science FoundationChina Postdoctoral Science Foundation [2017M610573]; Program for Guangdong Introducing Innovative and Entrepreneurial Teams [2017ZT07S096]
第一作者机构:[1]Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China[2]Sun Yat‐sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
共同第一作者:
通讯作者:
通讯机构:[1]Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China[2]Sun Yat‐sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China[*1]Sun Yatsen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China.[*2]Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
推荐引用方式(GB/T 7714):
Lui Zekun,Yu Kai,Zheng Jian,et al.Dysregulation, functional implications, and prognostic ability of the circadian clock across cancers[J].CANCER MEDICINE.2019,8(4):1710-1720.doi:10.1002/cam4.2035.
APA:
Lui, Zekun,Yu, Kai,Zheng, Jian,Lin, Huan,Zhao, Qi...&Zheng, Qichang.(2019).Dysregulation, functional implications, and prognostic ability of the circadian clock across cancers.CANCER MEDICINE,8,(4)
MLA:
Lui, Zekun,et al."Dysregulation, functional implications, and prognostic ability of the circadian clock across cancers".CANCER MEDICINE 8..4(2019):1710-1720