Expression and prognostic value of cholesterol homeostasis genes in hepatocellular carcinoma: A cohort study based on TCGA

Cholesterol metabolism is critical in cancer biology, yet its role in hepatocellular carcinoma (HCC) remains poorly understood. We investigated the expression and prognostic significance of cholesterol homeostasis genes in HCC to identify potential biomarkers for risk stratification. Using data from The Cancer Genome Atlas, we identified differentially expressed cholesterol-related genes (logFC ≥ 1.5, false discovery rate < 0.05), intersecting them with genes annotated in the Molecular Signatures Database. Prognostic biomarkers were evaluated using univariate and multivariate Cox regression. A predictive model was constructed to assess survival outcomes. Cholesterol homeostasis genes, particularly fatty acid-binding protein 5 (FABP5) and alcohol dehydrogenase 4 (ADH4), are key prognostic biomarkers in HCC. The proposed model provides a novel approach for predicting outcomes and may inform therapeutic strategies. Further studies are needed to validate these findings and explore their clinical utility. Nine cholesterol homeostasis genes were differentially expressed, including 6 upregulated (choline kinase alpha, FABP5, fatty acid synthase, farnesyl diphosphate synthase, mevalonate diphosphate decarboxylase, and squalene epoxidase) and 3 downregulated (ADH4, activating transcription factor 5, and arginine vasopressin receptor 1A). FABP5 and ADH4 emerged as independent prognostic factors: high FABP5 expression was associated with poor prognosis, while high ADH4 expression predicted improved survival. A prognostic model integrating FABP5 and ADH4 and clinical characteristics achieved a concordance index of 0.683, effectively stratifying patients into high-risk and low-risk groups (χ2 = 20.60, P < .001) with median survival times of 1135 and 2532 days, respectively.