a Division of Gastroenterology, Liyuan Hospital, Tongji Medical College , Huazhong University of Science and Technology , Wuhan China.
b Department of Hepatobiliary and Pancreas Surgery , Second Clinical Medical College of Jinan University (Shenzhen People's Hospital) , Shenzhen , Guangdong Province , China.
Chronobiol Int. 2019 Jul;36(7):906-918. doi: 10.1080/07420528.2018.1477792. Epub 2019 Apr 24.
Circadian rhythm describes the 24-h oscillation in physiology and behavior of living organisms and presents a timing controller for life activity. Studies in recent years have reported that the abnormal expression of clock genes is closely related to the development of common abdominal malignant tumors. The expression of the 14 kinds of clock genes in 6 abdominal malignant tumors from Cancer Genome Atlas (TCGA) data was integrated and analyzed using R and Perl programming languages to show the association between clock gene expression and prognosis of cancer patients. Analysis of TCGA data indicated that the overexpression of Per1-3, Cry2, CLOCK, NR1D2 and RORA with underexpression of Timeless and NPAS2 was associated with a favorable prognosis in kidney cancer. In liver cancer, high expressions of Cry2 and RORA were correlated with prolonged overall survival (OS) in patients, while high expressions of NPAS2 and Timeless were correlated with a poor survival. High expression of CLOCK was positively correlated with OS in colon cancer patients. High expression of Cry2 and low expression of DEC1 were associated with a favorable prognosis in pancreatic cancer patients, respectively. Most of these clock-genes expressions were closely related to the clinical stage and degree of tumor differentiation of patients. Aberrant clock gene expression is related to the biological characteristics of abdominal malignant tumors, which likely has a causal role in cancer development and survival.
昼夜节律描述了生物生理和行为的 24 小时波动，是生命活动的定时控制器。近年来的研究报告称，时钟基因的异常表达与常见腹部恶性肿瘤的发生发展密切相关。本研究应用 R 和 Perl 编程语言整合分析了癌症基因组图谱（TCGA）数据库中 6 种腹部恶性肿瘤的 14 种时钟基因的表达情况，以显示时钟基因表达与癌症患者预后之间的相关性。TCGA 数据分析表明，在肾癌中，Per1-3、Cry2、CLOCK、NR1D2 和 RORA 的过表达与 Timeless 和 NPAS2 的低表达与患者的预后良好相关。在肝癌中，Cry2 和 RORA 的高表达与患者的总生存期（OS）延长相关，而 NPAS2 和 Timeless 的高表达与预后不良相关。在结肠癌中，CLOCK 的高表达与患者的 OS 呈正相关。Cry2 的高表达和 DEC1 的低表达与胰腺癌患者的良好预后相关。这些时钟基因的表达大多与患者的临床分期和肿瘤分化程度密切相关。异常的时钟基因表达与腹部恶性肿瘤的生物学特征有关，可能在癌症的发生和生存中起因果作用。
