Identification of GINS2 prognostic potential and involvement in immune cell infiltration in hepatocellular carcinoma

Background: GINS2 has been reported to have prognostic value in several solid tumors other than hepatocellular carcinoma (HCC), and its influence on tumor immunity has not been investigated thus far. Methods: The transcriptome profiles were retrieved from two public databases, GEO and TCGA. The median GINS2 expression was considered as cutoff to define GINS2 ^high and GINS2 ^low groups and to obtain differentially expressed genes. These genes were then subjected to KEGG pathway and gene ontology (GO) analysis and to gene set enrichment analysis (GSEA). Survival analyses according to GINS2 level were performed utilizing Kaplan-Meier plotter. TIMER database was adopted to investigate associations between GINS2 level and infiltrating immunocytes, and the correlation between immunocyte-related gene expression and GINS2 level was evaluated via GEPIA database. A 236-patient validation cohort were applied to confirm the bioinformatic results of TCGA and TIMER database. Results: GINS2 is augmented in tumorous tissues of HCC patients compared with nontumor specimens, and GINS2-overexpressed patients have poorer overall survival (OS) and disease-specific survival (DSS) than those with low GINS2 expression in HCC (P = 0.009 and P = 0.002 respectively). Cell cycle and DNA replication were two main processes that enriched in tumor cells overexpressed GINS2 gene (NES = 1.848, P = 0.007; and NES = 1.907, P = 0.005, respectively). Moreover, GINS2 correlates positively with markers of activated CD8⁺ and CD4⁺ T cells, as well as exhausted T lymphocytes. Conclusions: HCC patients overexpressed GINS2 have poorer prognoses than those with low GINS2 expression, possibly as a result of the function of GINS2 in cell cycle and DNA replication as well the exhaustion of T lymphocytes.