ArticleDiscover oncology2025
Integrative analysis of cholesterol homeostasis reveals prognostic subtypes and immune features in clear cell renal cell carcinoma.
Article in Discover oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- CD276 promotes lipid metabolic reprogramming and regulates ferroptosis in clear cell renal cell carcinoma by upregulating FASN expression via SREBP1.Human cell · 2026Article
- A novel risk model of cholesterol metabolism-related mRNAs for predicting overall survival and immune signature in glioma based on machine learning and multi-omics data.Translational cancer research · 2026Article
- Integrative multi-omics analysis identifies a PTM-related immune signature and IRF9 as a driver in ccRCC.Frontiers in immunology · 2025Article
- HIF-2α inhibitors in clear cell renal cell carcinoma: a clinical pharmacy perspective on lipid metabolism, therapeutic management, and resistance strategies.Frontiers in medicine · 2025Review
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9 authors.
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Abstract
backgroundCholesterol is essential for tumor proliferation and progression. Cholesterol homeostasis has emerged as a key focus in cancer metabolism research. However, its role in clear cell renal cell carcinoma (ccRCC) remains poorly understood.
methodsRNA-sequencing and clinical data of ccRCC patients were obtained from The Cancer Genome Atlas and the Gene Expression Omnibus databases. The E-MTAB-1980 dataset served as an external validation cohort. Nonnegative Matrix Factorization was employed to construct the cholesterol homeostasis cluster. A cholesterol homeostasis signature (CHS) was constructed using the least absolute shrinkage and selection operator regression method to characterize the cholesterol metabolic status of ccRCC.
resultsTwo distinct molecular clusters associated with cholesterol homeostasis were identified, exhibiting divergent prognostic and immunological profiles. Analysis of immune cell infiltration revealed that Cluster C2 displayed immunosuppressive features, with enrichment of pro-tumor and immune-related pathways. The CHS was found to be predictive of both tumor immune status and clinical outcomes. Furthermore, we examined SREBF2, a key transcription factor in cholesterol regulation, and found that its high expression was associated with immune activation and favorable prognosis. Down-regulation of SREBF2 in ccRCC may lead to decreased cholesterol uptake and synthesis.
conclusionCholesterol homeostasis signature serves as a potential biomarker for prognosis, immune microenvironment status, and clinicopathological characteristics in ccRCC. Genes related to cholesterol homeostasis, such as SREBF2, may offer new therapeutic targets for immunomodulation in ccRCC.
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