Cholesterol metabolism-immune gene prognostic model in colorectal cancer

To investigate the association between serum cholesterol and the occurrence of colorectal cancer (CRC), and to construct a prognostic model for CRC based on cholesterol metabolism-related genes (CMG), clarifying the model's relationship with immune infiltration. Serum cholesterol levels were compared among 3865 participants (healthy individuals, patients with intestinal diseases, and cancer patients), and risk factors for CRC were analyzed. Meanwhile, cholesterol metabolism-related genes (CMGs) were screened from The Cancer Genome Atlas (TCGA) database. LASSO regression was employed to identify key genes and construct prognostic models. Based on the median risk score, patients with colon and rectal cancers were stratified into high-risk and low-risk groups to evaluate differences in prognosis and immune characteristics. CRC patients exhibited significantly higher serum cholesterol levels than other populations ( P < 0.001); total cholesterol was an independent risk factor for CRC (OR = 3.558). Prognostic models identified 9 key genes for colon adenocarcinoma (COAD) and 6 key genes for rectal adenocarcinoma (READ); overall survival was significantly lower in high-risk groups for both cancer types ( P < 0.05). Immune infiltration patterns differed: in COAD, high-risk patients showed higher ESTIMATE scores and TIDE scores, with immune scores positively correlating with regulatory T cells (Tregs), macrophages, and monocytes; in READ, immune scores positively correlated with M2 macrophages, while no significant differences in ESTIMATE scores or TIDE scores were observed between risk groups. High serum cholesterol is an independent risk factor for CRC. The prognostic model based on CMGs effectively predicts patient outcomes, offering potential therapeutic targets for clinical application.