Abstract
BACKGROUND: Hepatocellular carcinoma (HCC) remains a significant global health concern. Zinc finger protein 529 (ZNF529) may be associated with resistance to tyrosine kinase inhibitors (TKIs) in HCC. This study explored the expression of ZNF529 in HCC, its prognostic significance and its potential as a therapeutic target. We aimed to evaluate how the up-regulation of ZNF529 correlates with disease prognosis and drug resistance in HCC. METHODS: We analysed 4,556 HCC and 3,304 non-cancerous liver samples using publicly available RNA sequencing and tissue microarray data. The messenger RNA (mRNA) expression of ZNF529 was quantified, and a summary receiver operating characteristic (sROC) curve was used to assess its discriminatory ability. Immunohistochemistry was applied to confirm the protein expression levels. In addition, a single-cell analysis and survival analysis were performed to further evaluate the clinical relevance of ZNF529 expression in HCC. RESULTS: ZNF529 mRNA levels were significantly higher in HCC samples compared to non-cancerous liver tissue [standardized mean difference (SMD) =0.26, 95% confidence interval (CI): 0.14-0.38]. Immunohistochemistry results corroborated these findings with elevated protein levels, particularly in correlation with alpha-fetoprotein (AFP) expression. High expression of ZNF529 was associated with a significantly increased risk of poor prognosis in HCC [hazard ratio (HR) =1.94, 95% CI: 1.38-2.73]. ZNF529 was also up-regulated in TKI-resistant samples (SMD =0.63, 95% CI: 0.07-1.19). Functional enrichment analysis identified its involvement in RNA metabolism and cellular transport. CONCLUSIONS: Our findings suggest that ZNF529 is a promising prognostic biomarker for HCC. Its up-regulation correlates with poor prognosis, increased risk and resistance to TKI therapies. ZNF529 could serve as a potential therapeutic target, highlighting the need for further investigation into ZNF529-targeted therapies in HCC treatment.