ArticleDiscover oncology2024
A novel cholesterol metabolism-related ferroptosis pathway in hepatocellular carcinoma.
Article in Discover oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 6 citations in OpenAlex.
- An integrated multiomics-based risk model for predicting the prognosis and immune microenvironment status in patients with papillary thyroid carcinoma.Gland surgery · 2026Article
- A Prognostic Risk Model for Hepatocellular Carcinoma Integrating Ferroptosis and Metabolic Reprogramming Signatures.Journal of Cancer · 2026Article
- Identification and validation of a ferroptosis-related long non-coding RNA signature as a prognostic biomarker for hepatocellular carcinoma.Journal of gastrointestinal oncology · 2025Article
- Effective integration of multi-omics with prior knowledge to identify biomarkers via explainable graph neural networks.NPJ systems biology and applications · 2025Article
- HBx promotes tumorigenicity through RRM2-mediated autophagy in hepatocellular carcinoma.Cell & bioscience · 2024Article
- Ferroptosis-related prognostic model of mantle cell lymphoma.Open medicine (Warsaw, Poland) · 2024Article
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5 authors at 1 institution in 1 country.
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Abstract
backgroundEmerging studies have reported the contribution of cholesterol to hepatocellular carcinoma (HCC) progression. However, the specific role and mechanism of cholesterol metabolism on spontaneous and progressive HCC development from the point of view of ferroptosis are still worth exploring. The present study aimed to reveal a novel mechanism of cholesterol metabolism-related ferroptosis in hepatocellular carcinoma cells.
methodsTwo microarray datasets (GSE25097, GSE22058) related to HCC were downloaded from Gene Expression Omnibus (GEO) datasets. Metabolomics analysis was performed by ultra performance liquid chromatography - tandem mass spectrometer (UPLC-MS/MS). The cholesterol-related proteins were downloaded from HMBD. Ferroptosis-related genes were extracted from FerrDb database. Data sets were separated into two groups. GSE25097 was used to identify ferroptosis-related genes, and GSE22058 was used to verify results. During these processes, chemical-protein interaction (CPI), protein-protein interaction (PPI), the Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. Multivariate logistic regression analysis was used to test the associated pathway.
resultsWe identified 8 differentially expressed ferroptosis-related genes (HAMP, PTGS2, IL1B, ALOX15B, CDKN2A, RRM2, NQO1 and KIF20A) and 4 differentially expressed cholesterol-related genes (LCAT, CH25H, CEL and CYP7A1). Furthermore, based on the predicted results with STITCH, we identified indomethacin and IL1B as the essential node for cholesterol-mediated ferroptosis in hepatocellular carcinoma cell. Multivariate logistic regression analysis showed the activities of plasma IL1B in liver cancer patients enrolled have been significantly affected by the level of plasma cholesterol (P < 0.001) and the test result of IL1B is a predictor variable causing the changes of serum Fe levels (P < 0.001).
conclusionsOur findings shed new light on the association between cholesterol metabolism and ferroptosis in HCC, and suggest that IL1B is the necessary node for cholesterol to lead to ferroptosis process in HCC. Also, we identified the potential role of indomethacin in adjuvant therapy of HCC with complications of abnormal cholesterol metabolism.
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