A novel cholesterol metabolism-related ferroptosis pathway in hepatocellular carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38191842", "kind": "science-record", "revision": 3, "content_hash": "sha256:e425c0a04de90b1bad7d3b1cd7808f52d14fcdabb51c93bc7091c9e9a0ef171a", "created_at": "2026-11-01T19:20:06Z", "updated_at": "2026-11-01T22:10:59Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A novel cholesterol metabolism-related ferroptosis pathway in hepatocellular carcinoma.", "doi": "10.1007/s12672-023-00822-z", "pmid": "38191842", "authors": ["Weiwei Fang", "Jianyong Liu", "Fanguo Zhang", "Cheng Pang", "Xiying Li"], "journal": "Discover oncology", "year": 2024, "abstract": "BACKGROUND: Emerging 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.\nMETHODS: Two 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.\nRESULTS: We 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).\nCONCLUSIONS: Our 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.", "claims": [{"id": "claim-method", "statement": "Multivariate logistic regression analysis was used to test the associated pathway.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38191842", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Multivariate logistic regression analysis was used to test the associated pathway."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38191842", "locator": "sections[27] \"notes\" paragraph 1", "quote": "The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Multivariate logistic regression analysis showed that plasma cholesterol significantly affected plasma IL1B activity (P < 0.001), and IL1B was a predictor variable for changes in serum Fe levels (P < 0.001).", "kind": "quantitative", "target": {"value": 0.001, "unit": "p-value", "tolerance": null, "source": "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)."}, "evidence": [{"asset": "source:pmid:38191842", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "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)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Multivariate logistic regression analysis showed that plasma cholesterol significantly affected plasma IL1B activity (P < 0.001), and IL1B was a predictor variable for changes in serum Fe levels (P < 0.001).", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:38191842"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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