SOX11 as a potential prognostic biomarker in hepatocellular carcinoma linked to immune infiltration and ferroptosis.

Objective: SOX11 is expressed in numerous malignancies, including hepatocellular carcinomas (HCC), but its oncogenic function has not been elucidated. Here, we performed a comprehensive bioinformatics analysis of the Liver Hepatocellular Carcinoma (LIHC) dataset to investigate the function of SOX11 in tumorgenesis.

Methods: SOX11 expression data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were validated by immunohistochemistry (IHC). Co-expression, differential expression, and functional analyses utilized TCGA-LIHC, Timer 2.0, Metascape, GTEx, and LinkedOmics databases. Associations with immune infiltration, ferroptosis, and immune checkpoint genes were assessed. Genetic changes were explored via CBioPortal. Logistic regression, receiver operating characteristic curve (ROC), Kaplan-Meier analysis, and nomogram modeling evaluated associations with HCC clinicopathological features. SOX11's impact on proliferation and migration was studied in HepG2 and HuH7 cell lines.

Results: SOX11 was significantly elevated in HCC tumors compared to controls. SOX11-associated genes exhibited differential expression in pathways involving extracellular membrane ion channels. Significant associations were found between SOX11 levels, immune infiltration, ferroptosis, and immune checkpoint genes in HCC tissue. SOX11 levels correlated with HCC stage, histologic grade, and tumor status, and independently predicted overall and disease-specific survival. SOX11 expression effectively distinguished between tumor and normal liver tissue. Spearman correlations highlighted a significant relationship between SOX11 and ferroptosis-associated genes. Decreased SOX11 levels in HepG2 and HuH7 cells resulted in reduced proliferation and migration.

Conclusions: SOX11 was found to represent a promising biomarker within HCC diagnosis and prognosis together with being a possible drug-target.