CYP27A1 suppresses brain metastasis via ferroptosis in lung adenocarcinoma: a six-gene signature predicting the immunotherapy response and clinical outcomes.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41372758", "kind": "science-record", "revision": 3, "content_hash": "sha256:4a683fb0afb346fcead39f76b67a8dd3c23d825f1d295398ab975b8c3dc66878", "created_at": "2026-11-01T20:31:23Z", "updated_at": "2026-11-01T22:15:09Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "CYP27A1 suppresses brain metastasis via ferroptosis in lung adenocarcinoma: a six-gene signature predicting the immunotherapy response and clinical outcomes.", "doi": "10.1186/s12935-025-04112-2", "pmid": "41372758", "authors": ["Lu Xu", "Liyou Huang", "Zihao Liu", "Xiaojie Jiang", "Linchun Wen"], "journal": "Cancer cell international", "year": 2025, "abstract": "BACKGROUND: Lung adenocarcinoma (LUAD) brain metastasis has limited therapeutic options and a poor prognosis. This study aimed to identify molecular drivers, construct a prognostic model, and assess immunotherapy response.\nMETHODS: We integrated scRNA-seq data from 4 LUAD patients (GSE117570) and bulk RNA-seq data from the TCGA-LUAD cohort. Brain metastasis-associated differentially expressed genes (DEGs) were identified via Seurat. CellChat was used to analyse intercellular communication. A LASSO Cox prognostic model was constructed, and the function of CYP27A1 was validated in vitro.\nRESULTS: Six brain metastasis-linked genes (CD9, CYP27A1, HLA-DQB1, PEBP1, PECAM1, and TUBB) formed a risk model. High-risk patients had worse overall survival (HR = 1.91, p < 0.0001) and a reduced immunotherapy response. scRNA-seq revealed that M1 macrophages are involved in metastasis, with CYP27A1 significantly downregulated in LUAD cells. Functionally, CYP27A1 overexpression inhibited proliferation, migration, and invasion by inducing ferroptosis via iron homeostasis and lipid peroxidation (p < 0.05). High-risk patients presented lower immune scores/stromal components. A nomogram integrating the risk score, stage, and EGFR status showed robust 1-3 year predictive accuracy (AUC: 0.749-0.780).\nCONCLUSIONS: CYP27A1 is implicated as a suppressor of LUAD brain metastasis via ferroptosis. The six-gene model facilitates risk stratification, and macrophage-driven microenvironment remodelling informs potential immunotherapy strategies, advancing LUAD precision oncology.", "claims": [{"id": "claim-method", "statement": "The most important candidate genes were then selected via univariate Cox regression via the least absolute shrinkage and selection operator (LASSO) regression method, which was implemented via the R package glmnet(Version 4.1–10) with specific parameters configured for optimal selection.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41372758", "locator": "sections[11] \"Constructing a prognostic risk model for LUAD\" paragraph 2", "quote": "The most important candidate genes were then selected via univariate Cox regression via the least absolute shrinkage and selection operator (LASSO) regression method, which was implemented via the R package glmnet(Version 4.1–10) with specific parameters configured for optimal selection."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The single-cell RNA sequencing data analyzed in this study are available in the Gene Expression Omnibus (GEO) repository under accession number GSE117570. 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The bulk RNA sequencing and corresponding clinical data from The Cancer Genome Atlas Lung Adenocarcinoma (TCGA-LUAD) cohort were accessed via the Genomic Data Commons (GDC) portal (https://portal.gdc.cancer.gov/). Validation datasets GSE37745 and GSE50081 are available in the GEO repository under their respective accession numbers. Supplementary Table 1 is deposited in Figshare (DOI: 10.6084/m9.figshare.29208950). All other data supporting the findings of this study, including processed analytical results and experimental validation data, are available from the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Integrated scRNA-seq and bulk RNA-seq analysis with LASSO Cox regression produced a six-gene LUAD prognostic risk model, with high-risk patients having worse overall survival (HR = 1.91, p < 0.0001).", "kind": "quantitative", "target": {"value": 1.91, "unit": "hazard ratio", "tolerance": null, "source": "High-risk patients had worse overall survival (HR = 1.91, p < 0.0001) and a reduced immunotherapy response."}, "evidence": [{"asset": "source:pmid:41372758", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "We integrated scRNA-seq data from 4 LUAD patients (GSE117570) and bulk RNA-seq data from the TCGA-LUAD cohort."}, {"asset": "source:pmid:41372758", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "A LASSO Cox prognostic model was constructed, and the function of CYP27A1 was validated in vitro."}, {"asset": "source:pmid:41372758", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Six brain metastasis-linked genes (CD9, CYP27A1, HLA-DQB1, PEBP1, PECAM1, and TUBB) formed a risk model."}, {"asset": "source:pmid:41372758", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "High-risk patients had worse overall survival (HR = 1.91, p < 0.0001) and a reduced immunotherapy response."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Integrated scRNA-seq and bulk RNA-seq analysis with LASSO Cox regression produced a six-gene LUAD prognostic risk model, with high-risk patients having worse overall survival (HR = 1.91, p < 0.0001).", "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:41372758"], "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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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE117570", "GSE37745", "GSE50081"], "resolved_accessions": ["GSE117570", "GSE37745", "GSE50081"], "statements": ["The single-cell RNA sequencing data analyzed in this study are available in the Gene Expression Omnibus (GEO) repository under accession number GSE117570. The bulk RNA sequencing and corresponding clinical data from The Cancer Genome Atlas Lung Adenocarcinoma (TCGA-LUAD) cohort were accessed via the Genomic Data Commons (GDC) portal (https://portal.gdc.cancer.gov/). Validation datasets GSE37745 and GSE50081 are available in the GEO repository under their respective accession numbers. Supplementary Table 1 is deposited in Figshare (DOI: 10.6084/m9.figshare.29208950). All other data supporting the findings of this study, including processed analytical results and experimental validation data, are available from the corresponding author upon reasonable request."], "basis": "The paper names GSE117570, GSE37745, GSE50081 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. 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METHODS: We integrated scRNA-seq data from 4 LUAD patients (GSE117570) and bu", ".0001) and a reduced immunotherapy response. scRNA-seq revealed that M1 macrophages are involved in", "quality control filters were applied to the single-cell RNA sequencing data to remove low-quality cells and empty d"], "order_basis": "paper_text_order:359", "id": "assay:1"}, {"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ta from 4 LUAD patients (GSE117570) and bulk RNA-seq data from the TCGA-LUAD cohort. Brain metast", "tial gene screening for single-cell and bulk RNA-seq being considered statistically significant a", "trol filters were applied to the single-cell RNA sequencing data to remove low-quality cells and empty d"], "order_basis": "paper_text_order:416", "id": "assay:2"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["Ltd. (SNL-203), respectively. The cells were cultured in RPMI 1640 medium (Gibco, 11875085) or DMEM (", "lls/well in 25T flasks (Corning, 430168) and passaged every 48 h using 0.25% trypsin-EDTA (Gibco,", ". Cell culture Human lung cancer cell lines (A549 and H1299) and a normal bronchial epithelial"], "order_basis": "paper_text_order:3649", "id": "assay:3"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The most important candidate genes were then selected via univariate Cox regression via the least absolute shrinkage and selection operator (LASSO) regression method, which was implemented via the R package glmnet(Version 4.1–10) with specific parameters configured for optimal selection."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}