ZNF473 as a biomarker and potential therapeutic target in cancer: integrated bioinformatics and experimental evidence with a focus on hepatocellular carcinoma

<h4>Objective</h4>Zinc finger protein 473 (ZNF473) has been implicated as a regulatory factor in several cancer types; however, its precise biological functions and underlying mechanisms remain incompletely defined. This study aimed to evaluate the biological and clinical relevance of ZNF473 in cancer through integrated bioinformatics analyses in combination with cell-based experimental validation.<h4>Methods</h4>ZNF473 function was investigated using comprehensive bioinformatics approaches in combination with <i>in vitro</i> and <i>in vivo</i> experimental models.<h4>Results</h4>ZNF473 exhibited differential expression across a range of normal tissues and malignancies and was significantly upregulated in more than 10 cancer types. Analyses based on the Tumor-Immune System Interaction Database indicated that ZNF473 expression correlated with both molecular and immune subtypes in multiple cancers. Receiver operating characteristic analyses yielded an area under the curve exceeding 0.7 in 19 cancer types, suggesting moderate diagnostic performance. Kaplan-Meier and Cox regression analyses identified significant prognostic associations in four cancer types, with hepatocellular carcinoma (HCC) demonstrating the most consistent clinical relevance in this dataset. In HCC, elevated ZNF473 expression was associated with unfavorable clinicopathological features, altered immune cell infiltration profiles, and enrichment of PI3K/AKT-related signaling pathways. Functional assays further showed that ZNF473 knockdown reduced cellular proliferation and migration, together with decreased levels of phosphorylated AKT (p-AKT), in liver tumor models.<h4>Conclusion</h4>These findings support the role of ZNF473 as a clinically relevant biomarker candidate across cancers and suggest its involvement in HCC progression, potentially through activation of the AKT signaling pathway. The HCC-related findings should be interpreted cautiously, as further validation in established HCC models remains necessary.