Comprehensive characterization of SLC41A3 identifies it as an immune-related prognostic biomarker and therapeutic target in hepatocellular carcinoma.

BACKGROUND

Hepatocellular carcinoma (HCC) represents a highly aggressive cancer associated with substantial patient mortality. Members of the solute carrier (SLC) protein family have been implicated in facilitating tumor development and progression. However, the specific functions and relevance of SLC41A3 in the context of HCC pathogenesis are not well defined.

METHODS

Differentially expressed SLC genes were screened from the TCGA-LIHC cohort. Prognostic analysis identified independent prognostic factors. Diagnostic and prognostic models were constructed using machine learning and LASSO regression. Multi-omics analysis was employed to assess the expression characteristics, clinical relevance, spatial heterogeneity, and correlation with immune infiltration of SLC41A3. The biological function of SLC41A3 was validated through in vitro proliferation, colony formation, migration, and invasion assays, as well as an in vivo xenograft tumor model.

RESULTS

Sixty-nine SLC genes were differentially expressed in HCC, with eight identified as independent prognostic factors, including SLC41A3. The constructed diagnostic and prognostic models based on these genes demonstrated robust performance. SLC41A3 was highlighted as the most contributory feature in the diagnostic model. High expression of SLC41A3 was significantly associated with advanced clinicopathological features, poorer patient survival, specific spatial expression patterns, and altered immune cell infiltration in the tumor microenvironment. Functionally, knockdown of SLC41A3 significantly inhibited HCC cell proliferation, migration, invasion in vitro, and suppressed tumor growth in vivo.

CONCLUSION

This study identifies SLC41A3 as a novel prognostic biomarker and a promoter of HCC progression, with its function potentially linked to immune microenvironment modulation, suggesting its promise as a therapeutic target for HCC.