Overexpression of Taspase 1 Predicts Poor Prognosis in Patients with Hepatocellular Carcinoma.
Overexpression of Taspase 1 Predicts Poor Prognosis in Patients with Hepatocellular Carcinoma.
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Taspase 1 过度表达预示肝细胞癌患者预后不良
DOI：
10.2147/cmar.s296069
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发表时间：
2021
影响因子：
3.3
通讯作者：
Yang W
中科院分区：
文献类型：
--
作者：
Jiang J;Liu B;Liu R;Yang W
TASP 1（Taspase 1）是一种高度保守的蛋白酶，参与蛋白质的位点特异性水解。现有的研究已经揭示了TASP 1表达与肿瘤发生之间的联系。然而，有限的数据是关于肝细胞癌（HCC）的预后和TASP 1的功能。方法采用Western Blotting和qRT-PCR方法检测TASP 1在肝癌细胞系和临床标本中的表达。通过免疫组化进一步计算临床标本中TASP 1的表达，并使用Oncomine和UALCAN数据库分析HCC中TASP 1的mRNA水平。通过MEXPRESS和UALCAN显示TASP 1启动子甲基化修饰。采用Kaplan-Meier和考克斯回归分析评价TASP 1表达与临床患者术后预后的关系。通过Kaplan-Meier检验、GEPIA和UALCAN分析TASP 1对HCC预后的影响。此外，使用LinkedOmics鉴定了TASP 1的调节因子、激酶、miRNA和转录因子靶标。此外，cBioPortal用于检测TASP 1的遗传改变。最后，利用TIMER分析TASP 1与免疫细胞浸润的关系，并利用TISIDB分析TASP 1与3种免疫因子的相关性。结果TASP 1在肝癌细胞系和肝癌组织中表达增强。TASP 1的CNV和DNA甲基化发生改变。生存分析显示TASP 1高表达与总生存期（OS）相关。TASP 1在肝癌中的功能网络分析表明，TASP 1在肝癌中具有双链断裂修复、肽基苏氨酸修饰、纺锤体组装、肽基赖氨酸修饰和微管运动等功能。肝癌组织中TASP 1的表达与免疫细胞浸润及三种免疫因子密切相关。结论TASP 1可能是一个潜在的肝癌预后标志物，并通过多种机制调控肝癌的发生。
Background Taspase 1 (TASP1) is a highly conserved protease involved in site-specific proteolysis. Existing researches have revealed a link between TASP1 expression and carcinogenesis. However, limited data are available regarding the prognosis and functions of TASP1 in hepatocellular carcinoma (HCC). Methods Western Blotting and qRT-PCR were employed to evaluate the level of TASP1 in HCC cell lines and clinical specimens. TASP1 expression was further calculated in clinical specimens by immunohistochemistry and the mRNA level of TASP1 in HCC was analyzed using Oncomine and UALCAN databases. The TASP1 promoter methylation modification was shown via MEXPRESS and UALCAN. The association between TASP1 expression and postoperative prognosis was evaluated using Kaplan–Meier and Cox regression analysis in clinical patients. The effect of TASP1 on HCC prognosis was analyzed via Kaplan-Meier plotter, GEPIA and UALCAN. Additionally, the regulators, kinases, miRNA and transcription factor targets of TASP1 were identified using LinkedOmics. Moreover, cBioPortal was used to detect the genetic alteration of TASP1. Finally, TIMER was utilized to assess the relation between TASP1 and the immune cell infiltration, whereas the correlation of TASP1 with three immune factors was detected through TISIDB. Results TASP1 expression was increased in HCC cell lines and HCC tissues. CNV and DNA methylation of TASP1 were changed. Survival analysis revealed that high TASP1 expression was correlated with overall survival (OS). Functional network analysis about TASP1 in HCC showed that the double-strand break repair, peptidyl-threonine modification, spindle organization, peptidyl-lysine modification and microtubule-based movement were modulated. Furthermore, TASP1 expression revealed puissant relation to the infiltration of immune cells and three immune factors in HCC. Conclusion These data indicate that TASP1 may act as a potential prognostic marker in HCC and regulate HCC via multiple mechanisms.