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色氨酸2,3-双加氧酶促进肝细胞癌进展。

TDO Promotes Hepatocellular Carcinoma Progression.

作者信息

Li Shanbao, Li Lei, Wu Junyi, Song Fangbin, Qin Zhiwei, Hou Lei, Xiao Chao, Weng Junyong, Qin Xuebin, Xu Junming

机构信息

Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, People's Republic of China.

Department of General Surgery, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, People's Republic of China.

出版信息

Onco Targets Ther. 2020 Jun 19;13:5845-5855. doi: 10.2147/OTT.S252929. eCollection 2020.

Abstract

PURPOSE

Tryptophan 2,3-dioxygenase (TDO), encoded by the gene TDO2, is an enzyme that catalyses the first and rate-limiting step of tryptophan (Try) degradation in the kynurenine (Kyn) pathway in the liver. Recently, TDO has been demonstrated to be expressed in various human tumours, especially hepatocellular carcinoma (HCC). However, the role of TDO in HCC is still not very clear. Here, we studied the role of TDO in HCC.

METHODS

We demonstrated that TDO is overexpressed in human HCC tissues and is significantly correlated with malignant phenotype characteristics, including tumour size, tumour differentiation, vascular invasion, etc. Kaplan-Meier analysis showed a poor overall survival rate in patients with TDO-overexpressing tumours. In addition, the effects of TDO on HCC tumour growth and metastasis were detected both in vivo and in vitro. TDO overexpression facilitated HCC cell growth, invasion and migration.

CONCLUSION

Our results suggest that TDO positively regulates HCC proliferation and invasion and acts as a new prognostic biomarker of HCC.

摘要

目的

由TDO2基因编码的色氨酸2,3-双加氧酶(TDO)是一种催化肝脏中犬尿氨酸(Kyn)途径中色氨酸(Try)降解的第一步且为限速步骤的酶。最近,已证明TDO在多种人类肿瘤中表达,尤其是在肝细胞癌(HCC)中。然而,TDO在HCC中的作用仍不是很清楚。在此,我们研究了TDO在HCC中的作用。

方法

我们证明TDO在人类HCC组织中过表达,并且与恶性表型特征显著相关,包括肿瘤大小、肿瘤分化、血管侵犯等。Kaplan-Meier分析显示TDO过表达肿瘤患者的总生存率较差。此外,在体内和体外检测了TDO对HCC肿瘤生长和转移的影响。TDO过表达促进HCC细胞生长、侵袭和迁移。

结论

我们的结果表明TDO正向调节HCC的增殖和侵袭,并作为HCC的一种新的预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e568/7311207/93b4a8e3dc65/OTT-13-5845-g0001.jpg

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