Epigenetic and ncRNA Regulation of CBX2 in Liver Hepatocellular Carcinoma: A Comprehensive Multi-Omics Analysis for Understanding Biological Significance

Background and Objectives: Chromobox protein homolog 2 (CBX2), a member of the polycomb group of proteins that plays a role in chromatin remodeling, has been associated with multiple types of cancer. However, its characterization in liver hepatocellular carcinoma (LIHC) has not been fully elucidated. This study aims to systemically evaluate the expression, prognostic value, epigenetic regulation, and ncRNAs of CBX2 in LIHC. Materials and Methods: We performed a comprehensive in silico analysis to assess CBX2 expression at mRNA and protein levels, correlate its expression with clinical characteristics and prognosis, and explore DNA methylation and ncRNA-mediated regulatory networks. Multiple public databases (TIMER2.0, UALCAN, Human Protein Atlas, KM Plotter, MethSurv, miRNet, and ENCORI) were utilized to conduct expression, survival analysis, and construct a network encompassing miRNAs, lncRNAs, and pseudogenes. Results: CBX2 expression was found to be elevated in LIHC at both the mRNA and protein expression level. Increased CBX2 expression was closely linked with unfavorable clinical outcome. Methylation analysis indicated that various CpG sites, exhibiting both hypermethylation and hypomethylation patterns, were correlated with CBX2 expression and patient prognosis. Among the identified ncRNAs, hsa-miR-101-3p tended to be downregulated, whereas hsa-miR-222-3p was significantly upregulated in LIHC, and both were associated with CBX2 expression and clinical outcomes. The constructed ncRNA interaction network suggested potential associations among miRNA, lncRNAs, and pseudogenes that may be linked to tumor progression. Conclusions: Our results suggest that CBX2 was overexpressed in LIHC and may be associated with epigenetic alterations and ncRNA-related regulatory interactions. Its expression shows a relationship with clinical prognosis, suggesting that CBX2 could serve as a candidate biomarker. The proposed CBX2-associated ncRNA network represents a potential framework for further investigation, although additional experimental validation is required to confirm its biological and clinical relevance. Consequently, our findings suggest that CBX2 may serve as a potential prognostic biomarker and therapeutic target in LIHC, potentially influenced by specific epigenetic and post-transcriptional mechanisms.