Identification of Hub Genes in Liver Hepatocellular Carcinoma (LIHC) Using GEO Datasets: Insights into Molecular Mechanisms and Potential Therapeutic Targets

Abstract

Liver hepatocellular carcinoma (LIHC) is one of the most prevalent and lethal malignancies worldwide, necessitating the identification of novel biomarkers and therapeutic targets. In this study, we analyzed differentially expressed genes (DEGs) from two GEO datasets, GSE121248 and GSE101685, to identify hub genes potentially involved in LIHC pathogenesis. Using protein-protein interaction (PPI) networks and Venn diagram analysis, we identified four overlapping hub genes: VIPR1, ADAMTS13, CLEC4G, and CXCL14. Expression analysis via TCGA data revealed significantly lower expression levels of these genes in tumor tissues compared to normal tissues, suggesting their potential tumor-suppressive roles. Mutational analysis using OncoDB highlighted distinct genetic alterations in these hub genes, including missense and silent mutations, with ADAMTS13 showing the highest mutation frequency (1.3%). Promoter methylation analysis indicated significant hypermethylation of VIPR1 and CXCL14 in tumor tissues, implicating epigenetic regulation in LIHC progression. In contrast, CLEC4G and ADAMTS13 showed no significant methylation differences. Pathway enrichment analysis revealed the involvement of the hub genes in critical cancer-related pathways, such as platinum drug resistance and microRNAs in cancer. Drug sensitivity analysis identified significant correlations between ADAMTS13 and CLEC4G expression and responsiveness to various therapeutic agents, underscoring their relevance in treatment strategies. Our findings highlight the potential diagnostic, prognostic, and therapeutic significance of VIPR1, ADAMTS13, CLEC4G, and CXCL14 in LIHC. These genes warrant further investigation as biomarkers and targets for precision medicine in LIHC