Multi-Omics and Functional Analysis of BFSP1 as a Prognostic and Therapeutic Target in Liver Hepatocellular Carcinoma

Background and Objectives: Although beaded filament structural protein 1 (BFSP1) may be involved in oncogenic mechanisms, its clinical relevance and functional role in liver hepatocellular carcinoma (LIHC) remain unclear. This study examined the prognostic significance, regulatory mechanisms, and potential therapeutic implications of BFSP1 in LIHC. Materials and Methods: Comprehensive bioinformatics analysis was performed across multiple platforms using datasets derived from The Cancer Genome Atlas. Differential gene expression, DNA methylation, copy number variation, immune cell infiltration, drug sensitivity, and co-expression networks were systematically examined. Functional enrichment analyses of protein-protein and gene-gene interaction networks were conducted using STRING and GeneMANIA. Additionally, short interfering RNA-mediated knockdown and wound-healing assays were performed in HepG2 cells to evaluate BFSP1 function in vitro. Results: The results showed that BFSP1 mRNA expression was significantly upregulated in tissues from LIHC patients. Elevated BFSP1 levels were associated with poorer prognostic patterns, which were further supported by detailed clinicopathological subgroup analyses. Furthermore, BFSP1 expression was correlated with promoter hypomethylation and associated with patterns of tumor-infiltrating immune cells, including specific immune cell subtypes such as M1 and M2 macrophages. Integrative analyses revealed strong associations between BFSP1 and drug sensitivity, as well as a regulatory network encompassing genes involved in the cell cycle, DNA repair, and metabolic processes. Functional knockdown of BFSP1 significantly reduced HepG2 cell migration in vitro, as assessed by wound healing assay, with decreased wound closure at 24 h (11.0% vs. 16.5%) and 48 h (7.4% vs. 12.5%) compared with the control (p < 0.05, n = 6 biological replicates). Conclusions: In conclusion, these findings suggest that BFSP1 functions as a multifaceted prognostic biomarker and a potential therapeutic target for LIHC.