Cholesterol metabolism-immune gene prognostic model in colorectal cancer
- 1Huzhou Central Hospital, Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, No.1558, Sanhuan North Road, Wuxing Distric, Huzhou, Zhejiang 313000 People’s Republic of China
- 2School of Medicine, Tarim University, Alar, Xinjiang No. 1487 East Tarim Avenue, 843300 People’s Republic of China
- 3Zhejiang-France United Laboratory of Integrated Traditional Chinese and Modern Medicine in Colorectal Cancer, Huzhou, Zhejiang 313000 People’s Republic of China
Abstract
Objective: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s10020-026-01598-y.
Related
- Integrative multi-omics analysis of bile acid metabolism as a prognostic determinant in colorectal cancer
- Clinical Impact of Prognostic Immune and Nutritional Index on Short- and Long-term Outcomes of Older Patients with Colorectal Cancer.
- Matrix stiffness promotes colorectal cancer progression via Golgi-dependent cholesterol synthesis.
- Integrated Transcriptomic Analysis Identifies ENO3 as a Candidate Lactate Metabolism‐Associated Biomarker in Colorectal Cancer Metastasis
- Kinase-based molecular subtyping and a prognostic risk model in colorectal cancer with functional validation of PLK4
BibTeX
@article{xi2026cholesterol,
title = {{Cholesterol metabolism-immune gene prognostic model in colorectal cancer}},
author = {Yang Xi and Chu Jian and Xu Yang and Han Shuwen},
journal = {Molecular Medicine},
year = {2026},
month = aug,
doi = {10.1186/s10020-026-01598-y},
url = {https://doi.org/10.1186/s10020-026-01598-y},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Cholesterol metabolism-immune gene prognostic model in colorectal cancer
AU - Yang Xi
AU - Chu Jian
AU - Xu Yang
AU - Han Shuwen
PY - 2026
DA - 2026/08/11
JO - Molecular Medicine
DO - 10.1186/s10020-026-01598-y
UR - https://doi.org/10.1186/s10020-026-01598-y
AB - Objective: 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. Methods: 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. Results: 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. Conclusion: 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. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s10020-026-01598-y.
SN - 1076-1551
SN - 1528-3658
ER -