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在肝细胞癌中,西特龙激酶的低表达与患者预后不良相关。

Low expression of citron kinase is associated with poor patient outcomes in hepatocellular carcinoma.

作者信息

Zhang Huan-Qing, Wang Hui-Ju, He Xiang-Lei, Ru Guo-Qing, Song Shu-Shu, Pan Hong-Ying, Zhang Cheng-Wu, Mou Xiao-Zhou, Hu Zhi-Ming

机构信息

Department of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou 310014, China.

Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou 310014, China.

出版信息

Transl Cancer Res. 2020 Apr;9(4):2416-2423. doi: 10.21037/tcr.2020.03.58.

DOI:10.21037/tcr.2020.03.58
PMID:35117601
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8799013/
Abstract

BACKGROUND

Citron kinase (CIT) is a protein related to cytokinesis and is an important abscission regulator. However, the relationship between CIT and hepatocellular carcinoma (HCC) is unclear. The aim of this study was to investigate the expression CIT in HCC tissues, and explore the connection between this expression and clinicopathological characteristics of HCC.

METHODS

Immunohistochemistry staining on 235 HCC tissues and 96 non-tumorous liver tissues controls was performed to examine the CIT protein expression. We then analyzed the correlation between protein expression and clinicopathological parameters via χ tests, and we performed overall survival analyses via the Kaplan-Meier survival approach. Based on the online Oncomine Expression Array and UALCAN databases, we more broadly compared CIT mRNA expression between normal and HCC tissues. Finally, we compared CIT mRNA expression in these databases to protein expression in our study and explored potential sources for any observe differences.

RESULTS

Compared to normal tissues, CIT expression was significantly lower in HCC tissues. Low CIT expression was found to be related to gender, tumor size, Edmondson Grade, Microvascular invasion, serum AFP levels and poor overall survival. Based on the online databases, CIT mRNA expression was found to be high in HCC tissues and decreased in normal tissues. We hypothesize that this unexpected result is due to a negative feedback loop whereby low protein CIT levels mediate increased CIT mRNA levels.

CONCLUSIONS

Lower CIT protein levels are associated with a poorer prognosis in HCC patients, and lower CIT protein levels may mediate a negative feedback loop leading to increased CIT mRNA levels.

摘要

背景

西特龙激酶(CIT)是一种与胞质分裂相关的蛋白质,是一种重要的分裂调节因子。然而,CIT与肝细胞癌(HCC)之间的关系尚不清楚。本研究的目的是调查CIT在HCC组织中的表达,并探讨这种表达与HCC临床病理特征之间的联系。

方法

对235例HCC组织和96例非肿瘤性肝组织对照进行免疫组织化学染色,以检测CIT蛋白表达。然后通过χ检验分析蛋白表达与临床病理参数之间的相关性,并通过Kaplan-Meier生存法进行总生存分析。基于在线Oncomine表达阵列和UALCAN数据库,我们更广泛地比较了正常组织和HCC组织之间的CIT mRNA表达。最后,我们将这些数据库中的CIT mRNA表达与我们研究中的蛋白表达进行比较,并探讨观察到的差异的潜在来源。

结果

与正常组织相比,HCC组织中CIT表达明显较低。发现低CIT表达与性别、肿瘤大小、Edmondson分级、微血管侵犯、血清AFP水平及总生存较差有关。基于在线数据库,发现HCC组织中CIT mRNA表达较高,而在正常组织中降低。我们推测这一意外结果是由于负反馈回路,即低水平的CIT蛋白介导了CIT mRNA水平的升高。

结论

较低的CIT蛋白水平与HCC患者较差的预后相关,较低的CIT蛋白水平可能介导负反馈回路,导致CIT mRNA水平升高。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9270/8799013/b8018bbb37dd/tcr-09-04-2416-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9270/8799013/57a8b396e92e/tcr-09-04-2416-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9270/8799013/fa2cfaacaddb/tcr-09-04-2416-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9270/8799013/e94bc1e1dfa6/tcr-09-04-2416-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9270/8799013/56b51592a1e5/tcr-09-04-2416-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9270/8799013/c755b98b449b/tcr-09-04-2416-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9270/8799013/b8018bbb37dd/tcr-09-04-2416-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9270/8799013/57a8b396e92e/tcr-09-04-2416-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9270/8799013/fa2cfaacaddb/tcr-09-04-2416-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9270/8799013/e94bc1e1dfa6/tcr-09-04-2416-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9270/8799013/56b51592a1e5/tcr-09-04-2416-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9270/8799013/c755b98b449b/tcr-09-04-2416-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9270/8799013/b8018bbb37dd/tcr-09-04-2416-f6.jpg

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本文引用的文献

1
Citron kinase (CIT-K) promotes aggressiveness and tumorigenesis of breast cancer cells in vitro and in vivo: preliminary study of the underlying mechanism.柠檬酸盐激酶(CIT-K)在体外和体内促进乳腺癌细胞的侵袭和致瘤性:潜在机制的初步研究。
Clin Transl Oncol. 2019 Jul;21(7):910-923. doi: 10.1007/s12094-018-02003-9. Epub 2018 Dec 18.
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Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.全球癌症统计数据 2018:GLOBOCAN 对全球 185 个国家/地区 36 种癌症的发病率和死亡率的估计。
CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.
3
The changing epidemiology of liver diseases in the Asia-Pacific region.
亚太地区肝脏疾病的不断变化的流行病学。
Nat Rev Gastroenterol Hepatol. 2019 Jan;16(1):57-73. doi: 10.1038/s41575-018-0055-0.
4
Up-regulation of CIT promotes the growth of colon cancer cells.CIT的上调促进结肠癌细胞的生长。
Oncotarget. 2017 Jun 27;8(42):71954-71964. doi: 10.18632/oncotarget.18615. eCollection 2017 Sep 22.
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Global trends in the burden of liver cancer.肝癌负担的全球趋势。
J Surg Oncol. 2017 Apr;115(5):591-602. doi: 10.1002/jso.24518. Epub 2017 Mar 26.
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Investigating cytokinesis failure as a strategy in cancer therapy.研究胞质分裂失败作为癌症治疗的一种策略。
Oncotarget. 2016 Dec 27;7(52):87323-87341. doi: 10.18632/oncotarget.13556.
7
ASPM and CITK regulate spindle orientation by affecting the dynamics of astral microtubules.异常纺锤体微管相关蛋白(ASPM)和细胞侵袭与迁移激酶(CITK)通过影响星状微管的动力学来调节纺锤体方向。
EMBO Rep. 2016 Oct;17(10):1396-1409. doi: 10.15252/embr.201541823. Epub 2016 Aug 25.
8
Eph-mediated tyrosine phosphorylation of citron kinase controls abscission.Eph介导的西特龙激酶酪氨酸磷酸化控制细胞脱离。
J Cell Biol. 2016 Aug 29;214(5):555-69. doi: 10.1083/jcb.201602057. Epub 2016 Aug 22.
9
CIT, a gene involved in neurogenic cytokinesis, is mutated in human primary microcephaly.CIT,一个参与神经发生胞质分裂的基因,在人类原发性小头畸形中发生突变。
Hum Genet. 2016 Oct;135(10):1199-207. doi: 10.1007/s00439-016-1724-0. Epub 2016 Aug 12.
10
Biallelic Mutations in Citron Kinase Link Mitotic Cytokinesis to Human Primary Microcephaly.西特龙激酶的双等位基因突变将有丝分裂胞质分裂与人类原发性小头畸形联系起来。
Am J Hum Genet. 2016 Aug 4;99(2):501-10. doi: 10.1016/j.ajhg.2016.07.004. Epub 2016 Jul 21.