The prognostic value and functional role of CPSF3 in hepatocellular carcinoma

The identification of reliable biomarkers is critical for improving the diagnosis and treatment of hepatocellular carcinoma (HCC). Cleavage and polyadenylation specific factor 3 (CPSF3) has been implicated in RNA processing and tumor progression, but its role, clinical significance, and functional mechanisms in HCC remain unclear. In this study, we systematically evaluated CPSF3 expression and its potential role in HCC through multi-omics analyses and experimental validation. We observed significant CPSF3 upregulation in HCC tissues in multiple cohorts, and its upregulation was associated with advanced AJCC stage and poor survival. A prognostic nomogram incorporating CPSF3 and AJCC stage showed excellent predictive performance for HCC. CPSF3 demonstrated high diagnostic accuracy in HCC in TCGA and ICGC datasets. Functional experiments revealed that CPSF3 knockdown suppressed HCC cell proliferation, migration, and invasion while promoting apoptosis. Single-cell sequencing analysis revealed predominant CPSF3 expression in malignant cells and proliferating T cells in HCC. CPSF3 expression in HCC correlated with immune cell infiltration and was enriched in cell cycle and MAPK signaling pathways. These findings establish CPSF3 as a promising diagnostic and prognostic biomarker and highlight its potential as a therapeutic target for HCC.