SOX11 as a potential prognostic biomarker in hepatocellular carcinoma linked to immune infiltration and ferroptosis
Hongyu Chen, Qiangguo Ao, Yueling Wang, Yue Qian, Qingli Cheng, Wei Zhang
Abstract
<sec><b>Objective</b><i>SOX11</i> 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 <i>SOX11</i> in tumorgenesis.</sec><sec><b>Methods</b><i>SOX11</i> 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. <i>SOX11</i>’s impact on proliferation and migration was studied in HepG2 and HuH7 cell lines.</sec><sec><b>Results</b><i>SOX11</i> was significantly elevated in HCC tumors compared to controls. <i>SOX11</i>-associated genes exhibited differential expression in pathways involving extracellular membrane ion channels. Significant associations were found between <i>SOX11</i> levels, immune infiltration, ferroptosis, and immune checkpoint genes in HCC tissue. <i>SOX11</i> levels correlated with HCC stage, histologic grade, and tumor status, and independently predicted overall and disease-specific survival. <i>SOX11</i> expression effectively distinguished between tumor and normal liver tissue. Spearman correlations highlighted a significant relationship between <i>SOX11</i> and ferroptosis-associated genes. Decreased <i>SOX11</i> levels in HepG2 and HuH7 cells resulted in reduced proliferation and migration.</sec><sec><b>Conclusions</b><i>SOX11</i> was found to represent a promising biomarker within HCC diagnosis and prognosis together with being a possible drug-target.</sec>