UTP3: A Prognostic Marker in Hepatocellular Carcinoma and Its Role in Immunity and Epigenetics

Liver hepatocellular carcinoma (LIHC), a lethal malignancy with rising global incidence, urgently requires robust biomarkers for early diagnosis. Although dysregulated RNA-binding proteins contribute to oncogenesis, the role of UTP3 in LIHC prognosis, epigenetic modulation, and immune regulation has not been fully investigated. We conducted an integrative multi-omics analysis of TCGA and GTEx datasets to characterize UTP3 expression across cancers using DESeq. 2. Protein-level alterations were validated with CPTAC and HPA data. Clinical associations were evaluated via Cox regression and MethSurv for methylation analysis. The tumor immune microenvironment was assessed using ssGSEA and TIMER algorithms. CeRNA networks were built with RNA22, miRmap, and starBase tools, and functional studies were performed in Huh7 and HCCLM3 cell lines. Elevated UTP3 expression independently predicted unfavorable overall survival (HR = 1.574, p = 0.007) and was associated with advanced TNM stages (p < 0.05). Mechanistically, hypomethylation at cg26775961 (p = 0.011) promoted UTP3 upregulation, whereas the SNHG15/AL024498.1-miR-483-3p axis regulated its posttranscriptional levels (p < 0.001). Tumors with high UTP3 showed immunosuppressive features, including reduced cytotoxic cells infiltration (p = 0.008) and increased PD-L1 expression (p < 0.001). UTP3-interacting proteins (GRSF1 and NFKB1) enriched in NF-κB signaling (NES = 2.1, FDR = 0.03). A nomogram centered on UTP3 yielded a 1-year AUC of 0.693. This multi-omics study establishes UTP3 as a key regulator connecting epigenetic alterations, immune suppression, and tumor progression in LIHC.