Transcriptomics, lipidomics, and single-nucleus RNA sequencing integration: exploring sphingolipids in MASH-HCC progression.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40057751", "kind": "science-record", "revision": 3, "content_hash": "sha256:ec0bb47e22dfedb47fc87e57ac51e05a69d1297bb568b1ff8ca71f312d773442", "created_at": "2026-11-01T20:30:16Z", "updated_at": "2026-11-01T22:13:43Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Transcriptomics, lipidomics, and single-nucleus RNA sequencing integration: exploring sphingolipids in MASH-HCC progression.", "doi": "10.1186/s13578-025-01362-5", "pmid": "40057751", "authors": ["Jing Zeng", "Grayson Way", "Nan Wu", "Xixian Jiang", "Yun-Ling Tai", "Derrick Zhao", "Lianyong Su", "Qianhua Yan", "Xuan Wang", "Emily C Gurley", "Phillip B Hylemon", "Sayed Obaidullah Aseem", "Arun J Sanyal", "Jiangao Fan", "Huiping Zhou"], "journal": "Cell & bioscience", "year": 2025, "abstract": "BACKGROUND & AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses various conditions, ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH) and cirrhosis. MASLD is a significant risk factor for hepatocellular carcinoma (HCC) and is rapidly becoming the primary cause of liver transplantation. Dysregulated sphingolipid metabolism has been linked to the development of MASH-HCC. However, detailed insight into the sphingolipid profiles and cell type-specific changes in key genes involved in sphingolipid metabolism remains limited and forms the primary focus of this study.\nAPPROACHES & RESULTS: This study used the well-characterized diet-induced MASH-HCC mouse model (DIAMOND). Total RNA sequencing data, NanoString nCounter® Gene profiling, and single-nucleus RNA sequencing (snRNA-seq) GEO data (GSE225381) were used in characterizing gene regulation in MASH-HCC progression. Sphingolipids in the serum and liver were profiled using targeted lipidomics. RNA data analysis showed dysregulation of key genes involved in sphingolipid metabolism, including ceramide synthase 6 (Cers6), serine palmitoyltransferase long chain base subunit 2 (Sptlc2), sphingosine kinase 2 (SphK2), and sphingosine-1-phosphate receptor 1-3 (S1pr1-3) which paralleled significant changes in sphingolipid composition and levels in both serum and liver. Furthermore, TCGA-LIHC patient data were analyzed and potential prognostic genes for MASH-HCC were identified using univariate and multivariate Cox analysis. The multivariate Cox analysis underscored the prognostic significance of several genes related to sphingolipid metabolism, including CERS6, SPTLC2, and S1PR1.\nCONCLUSION: Our findings provided valuable insights into the role of sphingolipids in the progression of MASH to HCC. Specific serum and liver sphingolipid profiles may serve as valuable biomarkers for diagnosis and prognosis in MASH-HCC.", "claims": [{"id": "claim-method", "statement": "Non-parametric Mann-Whitney test was applied for variables that were not normally distributed, whereas normally distributed variables were assessed using an unpaired t-test with GraphPad Prism (version 8; GraphPad Software Inc., San Diego, CA). Through univariate Cox analysis, we identified several sphingolipid metabolism genes linked to overall survival (OS) in the TCGA-LIHC cohort, including SPTLC1, ACER3, CERS1, CERS6, CERS5, SPTLC2, S1PR1, and SGPP1 (Fig. 8C). A subsequent multivariate Cox analysis was conducted to further narrow down these genes into a prognostic signature comprising three genes: CERS6, SPTLC2, and S1PR1.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40057751", "locator": "sections[5] \"Statistical analysis\" paragraph 2", "quote": "Non-parametric Mann-Whitney test was applied for variables that were not normally distributed, whereas normally distributed variables were assessed using an unpaired t-test with GraphPad Prism (version 8; GraphPad Software Inc., San Diego, CA)."}, {"asset": "source:pmid:40057751", "locator": "sections[11] \"Profiling and establishing a sphingolipid gene signature in human HCC patients\" paragraph 2", "quote": "Through univariate Cox analysis, we identified several sphingolipid metabolism genes linked to overall survival (OS) in the TCGA-LIHC cohort, including SPTLC1, ACER3, CERS1, CERS6, CERS5, SPTLC2, S1PR1, and SGPP1 (Fig."}, {"asset": "source:pmid:40057751", "locator": "sections[11] \"Profiling and establishing a sphingolipid gene signature in human HCC patients\" paragraph 2", "quote": "8C)."}, {"asset": "source:pmid:40057751", "locator": "sections[11] \"Profiling and establishing a sphingolipid gene signature in human HCC patients\" paragraph 2", "quote": "A subsequent multivariate Cox analysis was conducted to further narrow down these genes into a prognostic signature comprising three genes: CERS6, SPTLC2, and S1PR1."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Detailed methods and datasets generated and/or analyzed during the current study are available in the Supplementary file.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40057751", "locator": "sections[18] \"notes\" paragraph 1", "quote": "Detailed methods and datasets generated and/or analyzed during the current study are available in the Supplementary file."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The high-risk group had significantly poorer overall survival than the low-risk group (p = 1.081e-03).", "kind": "quantitative", "target": {"value": 1.0, "unit": "p-value", "tolerance": null, "source": "Kaplan-Meier analysis demonstrated that the high-risk group had significantly poorer OS than the low-risk group (p = 1.081e-03)"}, "evidence": [{"asset": "source:pmid:40057751", "locator": "sections[11] \"Profiling and establishing a sphingolipid gene signature in human HCC patients\" paragraph 2", "quote": "Kaplan-Meier analysis demonstrated that the high-risk group had significantly poorer OS than the low-risk group (p = 1.081e-03)"}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The high-risk group had significantly poorer overall survival than the low-risk group (p = 1.081e-03).", "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:40057751"], "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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