Metabolic syndrome-related gene signature for prognosis and immune microenvironment prediction in hepatocellular carcinoma

Metabolic syndrome is a major risk factor for hepatocellular carcinoma (HCC) progression, yet the role of metabolic syndrome-related genes in HCC remains incompletely understood. Using bioinformatics approaches, we investigated the influence of these genes on HCC prognosis and tumor biology. Two distinct patient clusters (C1 and C2) were identified based on metabolic gene expression, with C2 exhibiting poorer survival, increased stemness, and higher risk scores. A risk model further revealed that high-risk patients had worse outcomes, elevated immunosuppressive cell infiltration, and distinct phenotypic features. Experimental validation via qRT-PCR confirmed upregulation of risk model genes (particularly KIAA1841 and TUBA1B) in HCC cell lines and patient blood samples. Notably, post-surgical declines in KIAA1841 and TUBA1B levels were observed. Our findings highlight the clinical relevance of metabolic syndrome-related genes in HCC, linking them to prognosis, tumor microenvironment remodeling, cancer stemness, and immunotherapy response.