A novel prognostic biomarker: is correlated with methylation and immune escape in liver hepatocellular carcinoma.

Background: Liver cancer remains one of the tricky malignancies nowadays. GINS complex subunit 3 (), part of the tetrameric complex, is significantly upregulated in many cancers, including liver hepatocellular carcinoma (LIHC). With the development of liver cancer treatment, immune and molecular targeted therapy gradually becomes a promising treatment. However, the key target for liver cancer is still indistinct. Herein, the underneath mechanism of was investigated to verify its role as a biomarker in LIHC.

Methods: Genomic expression, genetic alteration, and methylation analyses were obtained from The Cancer Genome Atlas (TCGA), Clinical Proteomic Tumor Analysis Consortium (CPTAC), The University of Alabama at Birmingham CANcer (UALCN), and Human Protein Atlas (HPA), cBioPortal, and MethSurv databases. Subsequently, the diagnostic and prognostic role of in LIHC were analyzed based on data from receiver operating characteristic (ROC), Kaplan-Meier plotter (KM-plotter), and univariate and multivariate cox regression analyses. The functional analyses were conducted with GeneMANIA and STRING databases, gene-gene, and protein-protein interaction (PPI) networks, Gene Ontology (GO) term, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Tumor Immune Estimation Resource (TIMER), Tumor-Immune System Interaction Database (TISIDB), and Gene Expression Profiling Interactive Analysis (GEPIA) were utilized to explore the internal connection with the immune escape.

Results: Through the analyses of genomic expression, was significantly upregulated in LIHC and positively correlated with higher T classification. ROC analysis indicated as a potential biomarker in the diagnosis of LIHC. KM-plotter, univariate and multivariate cox regression analyses both associated with poor prognosis in LIHC patients. genetic alteration, gene-gene interaction, PPI networks, and enrichment analysis further revealed that played a pivotal role in the progression of LIHC. Furthermore, hypermethylation of at different cytosine-guanine (CpG) sites was correlated with better or worse overall survival (OS) in LIHC and was also closely correlated with m6A modification. Moreover, results supported that could influence the tumor microenvironment and relate to the immune checkpoints.

Conclusions: Taken together, comprehensive analyses from this study supported as a novel targeted biomarker in LIHC.