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E3泛素连接酶TRIM4在预测肝细胞癌预后中的作用

Role of the E3 Ubiquitin Ligase TRIM4 in Predicting the Prognosis of Hepatocellular Carcinoma.

作者信息

Dong Zhao-Ru, Zhou Wei, Sun Dong, Yan Yu-Chuan, Yang Chun-Cheng, Yang Ya-Fei, Li Hai-Chao, Zhi Xu-Ting, Li Tao

机构信息

Department of General Surgery, Qilu Hospital, Shandong University, Jinan 250012, China.

出版信息

J Cancer. 2020 Apr 6;11(14):4007-4014. doi: 10.7150/jca.37164. eCollection 2020.

Abstract

The E3 ubiquitin ligase TRIM4 has been reported to regulate the assembly of the antiviral signalling complex, induce mitochondrial aggregation and sensitize cells to HO-induced death. However, the relationship between TRIM4 and human malignancies, including hepatocellular carcinoma (HCC), is unclear. In this study, we detected the expression of TRIM4 in 134 pairs of HCC tissues and peritumoural tissues and investigated the association of TRIM4 expression with the prognosis of HCC. We found that the TRIM4 expression was much lower in HCC tissues than in peritumoural tissues and was significantly associated with vascular invasion, tumour capsule and Hong Kong Liver Cancer (HKLC) stage. Univariate and multivariate analyses revealed that the TRIM4 expression was an independent prognostic factor for overall survival (OS) and recurrence-free survival (RFS) in our HCC cohort. Patients with higher TRIM4 expression had a lower incidence of intrahepatic recurrence and a higher OS rate (<0.001 and <0.01, respectively). These results were further validated in another independent cohort of 200 HCC patients. In conclusion, the TRIM4 level in HCC tissues is an independent prognostic factor for HCC patients. Close clinical monitoring is recommended for patients with low TRIM4 expression.

摘要

据报道,E3泛素连接酶TRIM4可调节抗病毒信号复合物的组装,诱导线粒体聚集,并使细胞对HO诱导的死亡敏感。然而,TRIM4与包括肝细胞癌(HCC)在内的人类恶性肿瘤之间的关系尚不清楚。在本研究中,我们检测了134对HCC组织和癌旁组织中TRIM4的表达,并研究了TRIM4表达与HCC预后的关系。我们发现,TRIM4在HCC组织中的表达远低于癌旁组织,且与血管侵犯、肿瘤包膜和香港肝癌(HKLC)分期显著相关。单因素和多因素分析显示,在我们的HCC队列中,TRIM4表达是总生存期(OS)和无复发生存期(RFS)的独立预后因素。TRIM4表达较高的患者肝内复发率较低,OS率较高(分别<0.001和<0.01)。这些结果在另一组200例HCC患者的独立队列中得到进一步验证。总之,HCC组织中的TRIM4水平是HCC患者独立的预后因素。建议对TRIM4表达低的患者进行密切的临床监测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d6c/7196267/a0f45b83172f/jcav11p4007g001.jpg

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