非小细胞肺癌中生物钟基因的研究。

Research on circadian clock genes in non-small-cell lung carcinoma.

机构信息

a Division of Gastroenterology, Liyuan Hospital, Tongji Medical College , Huazhong University of Science and Technology , Wuhan , China.

b Institute of Pathology, Tongji Hospital, Tongji Medical College , Huangzhong University of Science and Technology , Wuhan , China.

出版信息

Chronobiol Int. 2019 Jun;36(6):739-750. doi: 10.1080/07420528.2018.1509080. Epub 2019 Apr 24.

Abstract

Circadian clock genes have become a hot topic in cancer research in recent years, and more and more studies are showing that clock genes are involved in regulating cell proliferation cycle and apoptosis of malignant tumors, neuroendocrine and immune function, and other processes. Lung cancer is a malignant tumor with increasing incidence worldwide. The pathogenesis of lung cancer is extremely complicated and includes genetic factors, living environment, and smoking, and the occurrence of lung cancer is related to the regulation of many oncogenes and tumor suppressor genes. But there are few studies on clock genes in lung cancer. Studies on clock genes may help to better understand the mechanism of lung cancer development for an improved treatment. The expressions of all 14 kinds of clock genes in adenocarcinoma (ADC) and squamous cell carcinoma (SCC), two main kinds of non-small-cell lung cancer (NSCLC), were studied based on integration and analysis of data from The Cancer Genome Atlas (TCGA) to show the association between clock gene expression and prognosis of cancer patients. Analysis of TCGA data indicated that overexpression of Cry2, BMAL1, and RORA with underexpression of Timeless and NPAS2 was associated with a favorable prognosis of ADC, and the expression of NPAS2 was associated with the time of patient survival. Additionally, the expression of Cry2 was related to TNM stage. In SCC, high expression of DEC1 was correlated with poor overall survival in patients and the expression of Timeless was associated with the time of patient survival. In NSCLC, circadian clock genes constitute cancer circadian rhythm by interacting with each other, showing that asynchrony with normal tissues, which collectively controlling the occurrence and development of NSCLC.

摘要

近年来,生物钟基因已成为癌症研究的热门话题,越来越多的研究表明,生物钟基因参与调节恶性肿瘤的细胞增殖周期和细胞凋亡、神经内分泌和免疫功能等过程。肺癌是一种全球发病率不断增加的恶性肿瘤。肺癌的发病机制极其复杂,包括遗传因素、生活环境和吸烟等,肺癌的发生与许多癌基因和抑癌基因的调控有关。但是,关于肺癌中生物钟基因的研究较少。生物钟基因的研究可能有助于更好地了解肺癌的发展机制,从而改善治疗效果。通过对癌症基因组图谱(TCGA)的数据进行整合和分析,研究了两种主要的非小细胞肺癌(NSCLC)——腺癌(ADC)和鳞状细胞癌(SCC)中 14 种生物钟基因的表达情况,以显示时钟基因表达与癌症患者预后之间的关系。TCGA 数据分析表明,Cry2、BMAL1 和 RORA 的过表达以及 Timeless 和 NPAS2 的低表达与 ADC 的预后良好相关,而 NPAS2 的表达与患者的生存时间有关。此外,Cry2 的表达与 TNM 分期有关。在 SCC 中,DEC1 的高表达与患者的总生存率相关,而 Timeless 的表达与患者的生存时间有关。在 NSCLC 中,生物钟基因通过相互作用构成癌症生物钟节律,表现出与正常组织的不同步性,共同控制 NSCLC 的发生和发展。

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