Pan-cancer analysis of HOMER1 in hepatocellular carcinoma revealing diagnostic potential and immune landscape with experimental validation

Abstract

Objective

Homer scaffold protein 1 (HOMER1), a postsynaptic scaffold protein, regulates excitatory synapses and intracellular signaling and has been implicated in tumorigenesis. This study systematically evaluates the oncogenic roles of HOMER1 through pan-cancer bioinformatics analysis and functional validation in hepatocellular carcinoma (LIHC).

Methods

Multi-omics data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Tumor Immune Estimation Resource 2.0 (TIMER 2.0), cBioPortal, UALCAN, and other public databases were integrated to analyze HOMER1 expression profiles, prognostic relevance, epigenetic modifications, and immune infiltration. Drug sensitivity was assessed using Gene Set Cancer Analysis Lite (GSCALite) and DrugBank databases. Protein-protein interaction networks were constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and functionally annotated via Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. HOMER1 protein expression was validated by immunohistochemistry in LIHC tissues. Cellular assays, including Cell Counting Kit-8 (CCK-8), Transwell migration and invasion assays, wound healing assay, and quantitative polymerase chain reaction (qPCR), were performed to investigate the effects of HOMER1 knockdown on LIHC cell proliferation, migration, and invasion.

Results

Pan-cancer analysis revealed that HOMER1 exhibits cancer-type-specific dysregulation and is significantly associated with patient prognosis, DNA methylation, RNA modifications, immune cell infiltration, and immune checkpoint gene expression. HOMER1 expression correlated with anticancer drug sensitivity and was enriched in tumor-promoting pathways such as the peroxisome proliferator-activated receptor (PPAR) signaling pathway. In LIHC, HOMER1 was highly expressed, and its knockdown markedly suppressed hepatoma cell proliferation, migration, and invasion in vitro.

Conclusion

Our findings demonstrate that HOMER1 functions as a potential oncogene across multiple cancers and actively promotes malignant phenotypes in hepatocellular carcinoma. This study highlights HOMER1 as a promising prognostic biomarker and therapeutic target, providing new insights into cancer prognosis and immunotherapy strategies.