Up-regulated and interrelated expressions of GINS subunits predict poor prognosis in hepatocellular carcinoma.

Abstract

The GINS complex is one of the core components of the eukaryotic replicative helicase CMG (Cdc45–MCM helicase–GINS) complex that serves as the replicative helicase unwinding duplex DNA ahead of moving replication fork during chromosome duplication. Many studies have highlighted the important functions amongst GINS subunits in various cancers. Nevertheless, the functions and prognostic roles of distinct GINS subunits in hepatocellular carcinoma (HCC) were largely unexplored. In the present study, we reported the prognostic values of GINS subunits in HCC patients through analysis of several databases, including Oncomine, (TCGA), and Kaplan–Meier Plotter (KMPlotter). We found that mRNA expressions of all GINS subunits were significantly up-regulated in HCC tumor than in non-tumor liver tissues. Survival analysis revealed that elevated expression of individual GINS subunit predicts a poor overall survival (OS) in all HCC patients. When sorting the patients by gender, the correlation between elevated expression of individual GINS subunit and poor OS remains significant in male patient subgroup, but not in female patient subgroup. Additionally, we found that co-overexpression of all GINS subunits was significantly associated with a higher hazard ratio, suggesting the GINS complex may co-operate to promote HCC progression. Indeed, their expressions were highly correlated with each other in the same cohort and TRANSFAC analysis revealed that four transcription factors including C/EBPα, Oct-1, Sp1, and USF may serve as common transcription factors binding to the promoters of all four GINS subunits. Therefore, we propose that individual GINS subunit or GINS complex as a whole could be potential prognostic biomarkers for HCC.