Overexpression of Taspase 1 Predicts Poor Prognosis in Patients with Hepatocellular Carcinoma

Cancer Manag Res. 2021 Mar 16:13:2517-2537. doi: 10.2147/CMAR.S296069. eCollection 2021.

Abstract

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.

Keywords: TASP1; biological functional networks; hepatocellular carcinoma; prognosis.

Grants and funding

This study was supported by funds from the National Natural Science Foundation of China (grant numbers: #81873567 to Wenzhuo Yang) and Municipal Health Commission of Shanghai (#201640117 to Wenzhuo Yang).