Abstract / Summary
BRIX1 belongs to the Brix domain-containing protein family and participates in ribosomal assembly and in cell growth regulation. Nevertheless, a systematic pan-cancer assessment of BRIX1 expression and its clinical implications in liver hepatocellular carcinoma (LIHC) remains lacking. To characterize the biological and clinical significance of BRIX1, we conducted an integrated multi-omics analysis using datasets from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Human Protein Atlas (HPA). BRIX1 expression profiles, prognostic implications, genomic alterations, and immune-related associations were systematically evaluated across multiple malignancies. Gene Ontology (GO)/ Kyoto Encyclopedia of Genes and Genomes (KEGG), protein–protein interaction (PPI), and single-cell transcriptomic analyses were performed based on R software and several public databases. In vitro validation experiments were further carried out in LIHC tissues and cell lines. Pronounced upregulation of BRIX1 was observed across multiple tumor types, most notably in LIHC, and elevated expression was associated with poor prognosis in retrospective cohorts. In the TCGA LIHC cohort, BRIX1 remained independently associated with overall survival (OS) after multivariable adjustment. Integrated analyses demonstrated significant correlations between BRIX1 expression levels and tumor mutational burden (TMB), microsatellite instability (MSI), and immune-cell infiltration patterns. BRIX1-associated genes were primarily enriched in cell-cycle regulation, mitotic activity, and oncogenic signaling pathways. In addition, BRIX1 expression showed close relationships with immune regulatory signatures and potential responsiveness to immunotherapy. Functional experiments further showed that silencing BRIX1 inhibited the proliferative and invasive capacities of LIHC cells. BRIX1 is aberrantly overexpressed in LIHC and several additional malignancies and is closely linked to tumor progression, immune microenvironment characteristics, and adverse clinical outcomes. In LIHC, BRIX1 may represent a candidate prognostic biomarker and potential therapeutic target; however, these findings require independent prospective validation.