ArticleDiscover oncology2025
Multi-omics analysis reveals different cholesterol metabolism subtypes in colorectal cancer.
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 1 paper.
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Who cites it
1 citing paper in PubMed.
- Interplay Between Gut Microbiota and Cholesterol Metabolism in Colorectal Cancer.International journal of molecular sciences · 2026Review
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Authors and funding
11 authors.
Funding
Abstract
backgroundCholesterol metabolism (CM) plays a critical role in the progression of colorectal cancer (CRC), yet its molecular and immunological implications remain incompletely understood. Therefore, we aimed to identify CRC subtypes according to CM-related genes and reveal their distinct characteristics.
methodsBased on CM-related genes, we applied unsupervised clustering to classify CRC into two subtypes using transcriptomic data from TCGA and comprehensively compared their transcriptomic, genomic and clinical characteristics. We utilized single-cell RNA sequencing data and classified the samples into two subtypes and investigated the distinctions in the tumor microenvironment (TME) between these subtypes.
resultsTwo distinct CM subtypes were identified: Subtype A, characterized by cholesterol esterification and storage, was associated with inflammatory activation and cellular senescence. This subtype exhibited a poor prognosis and reduced predicted response to chemotherapy and immunotherapy. Tumor cells in Subtype A exhibited characteristics of epithelial-mesenchymal transition and angiogenesis. The TME in Subtype A contained higher infiltration of myeloid cells, fibroblasts, and pericytes, with dominant immunosuppressive tumor-associated macrophages (TAMs), especially TAM_SPP1, which interacted closely with Fibro_IL32, promoting immune exclusion. In contrast, Subtype B was marked by enhanced cholesterol catabolism and regulation. Tumor cells in this subtype displayed features of proliferation and stem-like properties. It showed a more active immune microenvironment with increased plasma cell infiltration and fewer immunosuppressive TAMs. Finally, we constructed a prognostic signature and validated its performance across multiple datasets.
conclusionsThese findings provide comprehensive insights into CM subtypes in CRC, highlighting their clinical significance and potential therapeutic implications.
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