<i>PSMD6</i> as a biomarker for hepatocellular carcinoma: A comprehensive bioinformatics analysis and <i>in vitro</i> validation

Hepatocellular carcinoma (HCC) is a lethal malignancy with limited diagnostic biomarkers. The present study aims to comprehensively investigate the expression, clinical prognostic significance, and potential mechanisms of PSMD6 in HCC through comprehensive bioinformatics analyses and <i>in vitro</i> experimental validation. <i>PSMD6</i> expression in HCC was analyzed using data from the UALCAN, SANGERBOX and TIMER databases. The association between PSMD6 expression and clinicopathological features, patient prognosis, and immune cell filtration was evaluated. Functional enrichment analyses (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes) were performed to identify PSMD6-related signaling pathways, and a protein-protein interaction (PPI) network was constructed using the BioGRID and STRING databases. Key findings from bioinformatics analyses were validated <i>in vitro</i> using reverse transcription-quantitative (RT-qPCR) and western blotting in HCC cell lines. <i>PSMD6</i> expression was significantly upregulated in HCC compared with adjacent normal tissues (P<0.001), which has been consistently validated by various databases and confirmed by <i>in vitro</i> experiments using RT-qPCR and western blotting. High PSMD6 expression was significantly associated with advanced tumor grade and patient age and served as an independent predictor of poor overall survival (P<0.001). In addition, <i>PSMD6</i> demonstrated high diagnostic accuracy for HCC (area under the curve=0.877). Moreover, <i>PSMD6</i> expression showed a positive correlation with the infiltration levels of CD4⁺ T cells and B cells in HCC (P<0.05), independent of tumor purity (P>0.05). Functional enrichment analysis indicated that PSMD6 was involved in critical oncogenic pathways, including the cell cycle. PPI network analysis revealed that <i>PSMD6</i> interact with several key proteins, such as <i>PSMC3, PSMD7</i> and <i>UCHL5</i> to achieve a regulatory function in HCC. In conclusion, <i>PSMD6</i> is significantly overexpressed in HCC and is strongly associated with tumor progression and poor prognosis. It represents a promising diagnostic biomarker and a potential therapeutic target for HCC.