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永恒基因与人类肺癌预后及临床特征的关联

Association of the Timeless Gene with Prognosis and Clinical Characteristics of Human Lung Cancer.

作者信息

Ye Jishi, Chen Jingli, Wang Juan, Xia Zhongyuan, Jia Yifan

机构信息

Department of Pain, Renmin Hospital of Wuhan University, 99 Zhang Road, Wuhan 430060, China.

Department of Anesthesiology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430060, China.

出版信息

Diagnostics (Basel). 2022 Nov 3;12(11):2681. doi: 10.3390/diagnostics12112681.

DOI:10.3390/diagnostics12112681
PMID:36359523
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9688960/
Abstract

(1) Background: As the most common malignant tumor type worldwide, it is necessary to identify novel potential prognostic biomarkers to improve the poor prognosis of lung cancer. The Timeless gene, a circadian rhythm-related gene, is associated with several types of cancer. However, studies analyzing the clinical significance of the Timeless gene in patients with lung cancer are currently limited. (2) Methods: In the present study, the expression levels and prognostic potential of the Timeless gene and its co-expressed genes in different subtypes of lung cancer were explored using multiple bioinformatics approaches. The correlations between the Timeless gene and its co-expressed genes were validated using A549 and NCI-H226 cells by transfecting them with expression vectors and analyses using Western blot and reverse transcription-quantitative PCR. (3) Results: The Oncomine and GEPIA database analyses indicated that the expression of the Timeless gene was significantly higher in lung cancer as compared to that in the normal tissue. Using the UALCAN database, significant differences in Timeless gene expression were determined among different stages of lung cancer and between genders. A Kaplan-Meier plotter analysis indicated that high expression of the Timeless gene was associated with poor overall survival (OS) and progression-free survival (PFS) of patients with lung cancer. In the cBioPortal and GEPIA database analyses, extra spindle pole bodies like 1 () was the top correlated gene of Timeless in patients with lung cancer. Similar to the Timeless gene, high expression of the gene was also associated with poor OS and PFS. Of note, overexpression of the Timeless gene increased the expression level of at both the mRNA and protein levels. (4) Conclusion: The present study explored the clinical significance of the Timeless gene and its correlated gene in patients with lung cancer, thereby providing a potential therapeutic target for lung cancer.

摘要

(1) 背景:作为全球最常见的恶性肿瘤类型,有必要识别新的潜在预后生物标志物以改善肺癌预后较差的状况。Timeless基因是一种与昼夜节律相关的基因,与多种癌症类型相关。然而,目前分析Timeless基因在肺癌患者中临床意义的研究有限。(2) 方法:在本研究中,使用多种生物信息学方法探讨了Timeless基因及其共表达基因在不同亚型肺癌中的表达水平和预后潜力。通过用表达载体转染A549和NCI-H226细胞,并使用蛋白质免疫印迹法和逆转录定量PCR进行分析,验证了Timeless基因与其共表达基因之间的相关性。(3) 结果:Oncomine和GEPIA数据库分析表明,与正常组织相比,Timeless基因在肺癌中的表达显著更高。使用UALCAN数据库,确定了Timeless基因在肺癌不同阶段和不同性别之间的表达存在显著差异。Kaplan-Meier生存曲线分析表明,Timeless基因的高表达与肺癌患者较差的总生存期(OS)和无进展生存期(PFS)相关。在cBioPortal和GEPIA数据库分析中,额外纺锤极体样蛋白1()是肺癌患者中与Timeless相关性最高的基因。与Timeless基因类似,该基因的高表达也与较差的OS和PFS相关。值得注意的是,Timeless基因的过表达在mRNA和蛋白质水平上均增加了的表达水平。(4) 结论:本研究探讨了Timeless基因及其相关基因在肺癌患者中的临床意义,从而为肺癌提供了一个潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/948a/9688960/2d2d736c1156/diagnostics-12-02681-g011.jpg
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本文引用的文献

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BMC Cancer. 2022 Jan 25;22(1):107. doi: 10.1186/s12885-022-09203-1.
2
The expression of the circadian gene TIMELESS in non-small-cell lung cancer and its clinical significance.昼夜节律基因TIMELESS在非小细胞肺癌中的表达及其临床意义。
Int J Clin Exp Pathol. 2020 Sep 1;13(9):2297-2304. eCollection 2020.
3
CK1α Collaborates with DOUBLETIME to Regulate PERIOD Function in the Circadian Clock.
CK1α 通过与 DOUBLETIME 协同作用调节生物钟中的 PERIOD 功能。
J Neurosci. 2018 Dec 12;38(50):10631-10643. doi: 10.1523/JNEUROSCI.0871-18.2018. Epub 2018 Oct 29.
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Nuclear cGAS suppresses DNA repair and promotes tumorigenesis.核 cGAS 抑制 DNA 修复并促进肿瘤发生。
Nature. 2018 Nov;563(7729):131-136. doi: 10.1038/s41586-018-0629-6. Epub 2018 Oct 24.
5
Clock genes polymorphisms in male bipolar patients with comorbid alcohol abuse.男性双相情感障碍合并酒精滥用患者的时钟基因多态性。
J Affect Disord. 2018 Dec 1;241:142-146. doi: 10.1016/j.jad.2018.07.080. Epub 2018 Jul 31.
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Cancer incidence and mortality patterns in Europe: Estimates for 40 countries and 25 major cancers in 2018.欧洲癌症发病率和死亡率模式:2018 年 40 个国家和 25 种主要癌症的估计值。
Eur J Cancer. 2018 Nov;103:356-387. doi: 10.1016/j.ejca.2018.07.005. Epub 2018 Aug 9.
7
[Timeless promotes the proliferation of hepatocellular carcinoma cell by reprogramming of glucose metabolism].[永恒因子通过重编程葡萄糖代谢促进肝癌细胞增殖]
Zhonghua Zhong Liu Za Zhi. 2018 Jul 23;40(7):499-505. doi: 10.3760/cma.j.issn.0253-3766.2018.07.004.
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Knockdown of timeless Disrupts the Circadian Behavioral Rhythms in Laodelphax striatellus (Hemiptera: Delphacidae).敲低timeless基因会破坏灰飞虱(半翅目:飞虱科)的昼夜行为节律。
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Altered circadian genes expression in breast cancer tissue according to the clinical characteristics.根据临床特征改变乳腺癌组织的昼夜节律基因表达。
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A role for the clock period circadian regulator 2 gene in regulating the clock gene network in human oral squamous cell carcinoma cells.生物钟周期昼夜调节因子2基因在调控人口腔鳞状细胞癌细胞生物钟基因网络中的作用。
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