Role of galectin-3 in enhancing HBV replication and predicting hepatocellular carcinoma: mechanistic insights and clinical implications

Abstract Background Hepatocellular carcinoma (HCC) is a common malignancy globally, often associated with hepatitis B virus (HBV) infection. Galectin-3 (Gal-3), a multifunctional β-galactoside-binding protein, has been implicated in liver diseases. This study aimed to investigate the role of Gal-3 in HBV replication and hepatic inflammation and evaluate its potential as an early diagnostic biomarker for HCC. Methods An HBV replication model was established in HepG2 cells. The impact of Gal-3 on HBV DNA replication and the expressions of HBsAg and HBeAg were analyzed using quantitative PCR and ELISA. Western blot analysis was performed to investigate the influence of Gal-3 on inflammatory signaling pathways. Serum levels of Gal-3 in patients with various liver diseases were measured by ELISA, and their correlation with liver inflammation markers was evaluated. Results In the HBV-replicating HepG2 cells, Gal-3 overexpression significantly increased HBV DNA replication, HBsAg, and HBeAg expression, while knockdown had the opposite effect. Gal-3 was involved in the regulation of inflammatory signaling pathway proteins, including NF-κB-p65, IL-1β, NLRP3, and caspase-1. Analysis of serum samples from patients revealed that Gal-3 levels were significantly elevated in various liver diseases compared to the control group, and there was a linear correlation between Gal-3 expression and clinical markers such as ALT, AST, and ALP. A diagnostic model incorporating Gal-3 and WBC was established, demonstrating superior predictive capability for HCC compared to AFP. Conclusion Gal-3 plays a crucial role in HBV replication and hepatic inflammation and its serum levels are closely associated with the severity of liver diseases. Moreover, Gal-3 shows promise as a diagnostic biomarker for early detection of HCC. Further research is needed to validate Gal-3's diagnostic potential and explore its suitability as a therapeutic target.