Abstract
BACKGROUND: While systemic cholesterol levels are generally associated with cancer risk and progression in various tumors, studies of cholesterol de novo synthesis by cancer cells in various tumor settings were limited. This meta-analysis aims to provide a comprehensive understanding of the role of cholesterol de novo synthesis pathway in cancer, focusing on key markers related with this metabolic reprogramming in cancer tissues. METHODS: A systematic review and meta-analysis were conducted using data from multiple databases, including PubMed, EMBASE, and Cochrane Library. Studies were included if they examined the expression of cholesterol synthesis markers in solid tumors and reported hazard ratios (HRs) for overall survival (OS), disease-free survival (DFS), or recurrence-free survival (RFS). Data extraction and quality assessment were performed by two independent researchers. Pooled HRs and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models. RESULTS: Twenty studies involving 4,343 patients were included. High expression of cholesterol metabolism and esterification markers was significantly associated with worse prognosis in overall survival (OS: HR 2.38, 95% CI 1.97-2.87, p < 0.0001) and disease-free survival (DFS: HR 2.44, 95% CI 1.69-3.51, p < 0.0001). However, no significant association was observed for recurrence-free survival (RFS: HR 0.95, 95% CI 0.28-3.24, p = 0.9), with substantial heterogeneity (I² = 89%). Elevated expressions of enzymes correlated with more aggressive tumor characteristics, including lymph node metastasis and larger tumor size. CONCLUSIONS: High expression of cholesterol metabolism markers in solid tumors is linked to poorer survival and aggressive disease features. Among these, SQLE and SOAT1 stand out as the most robust predictors and potential therapeutic targets, emphasizing the critical role of cholesterol metabolic reprogramming in cancer progression.