Identification of potential blood biomarkers of coronary artery disease using a cuproptosis gene set.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41204370", "kind": "science-record", "revision": 4, "content_hash": "sha256:1dcac4da61e0f6726beeb016621533ebd0829fd8eccced04129c97139d2a24f4", "created_at": "2026-11-01T20:31:14Z", "updated_at": "2026-11-01T22:57:25Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of potential blood biomarkers of coronary artery disease using a cuproptosis gene set.", "doi": "10.1186/s40001-025-03276-x", "pmid": "41204370", "authors": ["Jia Li", "Kaibo Lei", "Ping Hu", "Zhanwei Zhu", "Lin Wang", "Can-E Tang", "Fanyan Luo"], "journal": "European journal of medical research", "year": 2025, "abstract": "PURPOSE: To investigate whether cuproptosis-related genes contribute to coronary artery disease (CAD) pathogenesis and to develop a robust, blood-based diagnostic model.\nPATIENTS AND METHODS: Whole-blood transcriptome profiles (GSE180081, GSE180082) were retrieved from the GEO database. After batch-effect correction (limma::removeBatchEffect) and quantile normalization, differentially expressed genes (DEGs) between CAD patients (n = 521) and controls (n = 191) were identified with FDR < 0.05 and |log2FC|≥ 1. Consensus clustering (ConsensusClusterPlus, k = 2) on 19 cuproptosis genes stratified patients into high- and low-cuproptosis activity groups. DEGs between these clusters were intersected with the CAD-DEG list to yield 818 cuproptosis-linked DEGs. A five-gene diagnostic signature (HIST1H4E, IL6ST, LST1, RN7SKP45, and SNORD50B) was selected by LASSO regression and modeled with logistic regression. Immune infiltration, ceRNA networks, and druggability were further analyzed. Local RT-qPCR in an independent cohort (12 CAD, 12 controls) confirmed expression trends.\nRESULTS: We identified 818 differentially expressed genes that were common to the CAD and cuproptosis gene sets, and these principally represented the cell-substrate junction and the positive regulation of leukemia. Furthermore, HIST1H4E, IL6ST, RN7SKP45, LST1, and SNORD50B were found to be potentially useful for the diagnosis of CAD using our diagnostic model. These genes were also found to be closely associated with immune modification. Further validation revealed that HIST1H4E, IL6ST, and LST1 are very likely to be potential biomarkers.\nCONCLUSION: We constructed a diagnostic prediction model based on cuproptosis-related genes using whole-blood transcriptome data. Our results identify HIST1H4E, IL6ST, and LST1 as potential biomarkers for CAD risk assessment. These findings provide a novel basis for the prediction, prevention, and individualized treatment of CAD.", "claims": [{"id": "claim-method", "statement": "The limma [19] package was used to identify differentially expressed genes, and ROC curve analysis was performed using the pROC [28] package.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41204370", "locator": "sections[14] \"Statistical analysis\" paragraph 2", "quote": "The limma [19] package was used to identify differentially expressed genes, and ROC curve analysis was performed using the pROC [28] package."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. These data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE180081 (GPL14761), https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE180082 (GPL14761).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41204370", "locator": "sections[34] \"notes\" paragraph 1", "quote": "Publicly available datasets were analyzed in this study. These data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE180081 (GPL14761), https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE180082 (GPL14761)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "HIST1H4E, IL6ST, and LST1 were identified as cuproptosis-associated genes that are biomarkers of CAD and were used to construct a new CAD prediction model.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:41204370", "locator": "sections[28] \"Conclusion\" paragraph 2", "quote": "In summary, we identified HIST1H4E, IL6ST, and LST1 as genes that are associated with cuproptosis and are biomarkers of CAD and used them to construct a new CAD prediction model."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "HIST1H4E, IL6ST, and LST1 were identified as cuproptosis-associated genes that are biomarkers of CAD and were used to construct a new CAD prediction model.", "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:41204370"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE180081"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE180081"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:41204370", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s40001-025-03276-x", "sha256": "sha256:916b90adbc43db1cbee23c1ee306b4592cc9eb3faf8d884b69328a9e2d0bf51a", "bytes": 39521, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s40001-025-03276-x", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12595643", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE180081", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE180081", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE180081", "version": null, "note": "Publicly available datasets were analyzed in this study. 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Local RT-qPCR in an independent cohort (12 CAD, 12 control", "druggability were further analyzed. Local RT-qPCR in an independent cohort (12 CAD, 12 control", "ays identified in the GO analysis (Fig. 3D). RT-qPCR analysis of the expression of the identified", "was extracted from peripheral monocytes, and RT-qPCR was performed to measure the expression of L"], "order_basis": "paper_text_order:1054", "id": "assay:1"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["more strongly linked to immune pathways than apoptosis or ferroptosis. Their unique association wit", "hroughout the pathogenesis of CAD [49]. 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