Prognostic implication of cuproptosis related genes associates with immunity in Ewing's sarcoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36871208", "kind": "science-record", "revision": 2, "content_hash": "sha256:9a933c376c2f26b47e3f6aac46f4dae1b0ad544c8dd52dd0e49349c6cc978e22", "created_at": "2026-11-01T19:01:30Z", "updated_at": "2026-11-01T21:30:17Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Prognostic implication of cuproptosis related genes associates with immunity in Ewing's sarcoma.", "doi": "10.1016/j.tranon.2023.101646", "pmid": "36871208", "authors": ["Qingbo Li", "Xiao Xu", "Xiejia Jiao"], "journal": "Translational oncology", "year": 2023, "abstract": "Growing evidence demonstrated that cuproptosis play critical roles in human cancers. We aimed to identify the roles of cuproptosis related genes (CRGs) in prognosis and immunity of Ewing's sarcoma. The data of GSE17674 and GSE63156 were obtained from GEO. The expression of 17 CRGs and immune cells were explored, then correlation was analyzed. Based on CRGs, two molecular clusters were identified by consensus clustering algorithm. KM survival and IME features including immune cells, immune response, checkpoint genes between clusters were evaluated. NFE2L2, LIAS, and CDKN2A were screened out as prognostic signatures by univariate, LASSO and step regression. A risk model was established, and validated by KM method with p = 0.0026, and perfect AUC values. The accuracy of risk model was also well validated in external dataset. A nomogram was constructed and evaluated by calibration curves and DCA. Low level of immune cells, immune response, and enriched checkpoint genes were found in high-risk group. GSEA of signatures and GSVA of ES-related pathways revealed the potential molecular mechanism involved in ES progression. Several drugs showed sensitivity to ES samples. DEGs between risk groups were screened out, and function enrichment was conducted. Finally, scRNA analysis of GSE146221 was done. NFE2L2, and LIAS played crucial role in the evolution of ES by pesudotime and trajectory methods. Our study provided new aspects for further research in ES.", "claims": [{"id": "claim-method", "statement": "Univariate Cox regression (p < 0.06) was applied to generate the prognostic CRGs. Then LASSO algorithm with lambda.min was used to reduce variables [20]. Finally, CRGs signatures were screened out by multivariate step regression with the lowest Akaike information criterion (AIC) via \"survival\" package [21].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36871208", "locator": "sections[6] \"Survival analysis and risk model construction\" paragraph 2", "quote": "Univariate Cox regression (p < 0.06) was applied to generate the prognostic CRGs. Then LASSO algorithm with lambda.min was used to reduce variables [20]. Finally, CRGs signatures were screened out by multivariate step regression with the lowest Akaike information criterion (AIC) via \"survival\" package [21]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data used in this study are available in publicly in GEO.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36871208", "locator": "sections[29] \"Data availability\" paragraph 2", "quote": "The data used in this study are available in publicly in GEO."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A risk model was established, and validated by KM method with p = 0.0026, and perfect AUC values.", "kind": "quantitative", "target": {"value": 0.0026, "unit": "p-value", "tolerance": null, "source": "A risk model was established, and validated by KM method with p = 0.0026, and perfect AUC values."}, "evidence": [{"asset": "source:pmid:36871208", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "A risk model was established, and validated by KM method with p = 0.0026, and perfect AUC values."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A risk model was established, and validated by KM method with p = 0.0026, and perfect AUC values.", "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:36871208"], "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:GSE146221"], "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:GSE146221"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36871208", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1016/j.tranon.2023.101646", "sha256": "sha256:2e644e663bd2720cd19b2e256b6f6b4d0ee25e860d06dc6f2fe5630b063bd789", "bytes": 52921, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1016/j.tranon.2023.101646", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10006858", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE146221", "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=GSE146221", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE146221", "version": null, "note": "The data used in this study are available in publicly in GEO.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data used in this study are available in publicly in GEO.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4368462", "GSM4368463", "GSM4368464"], "sample_count": 3, "group_sizes": null, "group_sizes_basis": null, "platform": "21290;24676", "taxon": "Homo sapiens", "title": "Single cell transcriptomics of Ewing Sarcoma cell lines", "resolution_checked_at": "2026-11-01T18:46:34Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE17674", "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=GSE17674", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE17674", "version": null, "note": "The data used in this study are available in publicly in GEO.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data used in this study are available in publicly in GEO.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM440999", "GSM441000", "GSM441001", "GSM441002", "GSM441003", "GSM441004", "GSM441005", "GSM441006", "GSM441007", "GSM441008", "GSM441009", "GSM441010", "GSM441011", "GSM441012", "GSM441013", "GSM441014", "GSM441015", "GSM441016", "GSM441017", "GSM441018", "GSM441019", "GSM441020", "GSM441021", "GSM441022", "GSM441023", "GSM441024", "GSM441025", "GSM441026", "GSM441027", "GSM441028", "GSM441029", "GSM441030", "GSM441031", "GSM441032", "GSM441033", "GSM441034", "GSM441035", "GSM441036", "GSM441037", "GSM441038", "GSM441039", "GSM441040", "GSM441041", "GSM441042", "GSM441044", "GSM441045", "GSM441046", "GSM441047", "GSM441048", "GSM441049", "GSM441050", "GSM441051", "GSM441052", "GSM441053", "GSM441054", "GSM441055", "GSM441056", "GSM441057", "GSM441058", "GSM441059", "GSM441060", "GSM441061"], "sample_count": 62, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Inflammatory gene profiling of Ewing sarcoma family of tumors (set B)", "resolution_checked_at": "2026-11-01T18:06:43Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE63156", "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=GSE63156", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE63156", "version": null, "note": "The data used in this study are available in publicly in GEO.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data used in this study are available in publicly in GEO.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1542380", "GSM1542381", "GSM1542382", "GSM1542383", "GSM1542384", "GSM1542385", "GSM1542386", "GSM1542387", "GSM1542388", "GSM1542389", "GSM1542390", "GSM1542391", "GSM1542392", "GSM1542393", "GSM1542394", "GSM1542395", "GSM1542396", "GSM1542397", "GSM1542398", "GSM1542399", "GSM1542400", "GSM1542401", "GSM1542402", "GSM1542403", "GSM1542404", "GSM1542405", "GSM1542406", "GSM1542407", "GSM1542408", "GSM1542409", "GSM1542410", "GSM1542411", "GSM1542412", "GSM1542413", "GSM1542414", "GSM1542415", "GSM1542416", "GSM1542417", "GSM1542418"], "sample_count": 39, "group_sizes": null, "group_sizes_basis": null, "platform": "5175", "taxon": "Homo sapiens", "title": "Gene Expression Profiling of Ewing Sarcoma Tumors Reveals the Prognostic Importance of Tumor-Stromal Interactions [EuroEwing]", "resolution_checked_at": "2026-11-01T18:46:34Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE68776", "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=GSE68776", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE68776", "version": null, "note": "The data used in this study are available in publicly in GEO.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data used in this study are available in publicly in GEO.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1681080", "GSM1681081", "GSM1681082", "GSM1681083", "GSM1681084", "GSM1681085", "GSM1681086", "GSM1681087", "GSM1681088", "GSM1681089", "GSM1681090", "GSM1681091", "GSM1681092", "GSM1681093", "GSM1681094", "GSM1681095", "GSM1681096", "GSM1681097", "GSM1681098", "GSM1681099", "GSM1681100", "GSM1681101", "GSM1681102", "GSM1681103", "GSM1681104", "GSM1681105", "GSM1681106", "GSM1681107", "GSM1681108", "GSM1681109", "GSM1681110", "GSM1681111", "GSM1681112", "GSM1681113", "GSM1681114", "GSM1681115", "GSM1681116", "GSM1681117", "GSM1681118", "GSM1681119", "GSM1681120", "GSM1681121", "GSM1681122", "GSM1681123", "GSM1681124", "GSM1681125", "GSM1681126", "GSM1681127", "GSM1681128", "GSM1681129", "GSM1681130", "GSM1681131", "GSM1681132", "GSM1681133", "GSM1681134", "GSM1681135", "GSM1681136", "GSM1681137", "GSM1681138", "GSM1681139", "GSM1681140", "GSM1681141", "GSM1681142", "GSM1681143", "GSM1681144", "GSM1681145", "GSM1681146", "GSM1681147", "GSM1681148", "GSM1681149", "GSM1681150", "GSM1681151", "GSM1681152", "GSM1681153"], "sample_count": 74, "group_sizes": null, "group_sizes_basis": null, "platform": "5175", "taxon": "Homo sapiens", "title": "Exon array profiles of primary human Ewing sarcoma tumors", "resolution_checked_at": "2026-11-01T18:06:44Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE146221 not downloaded", "asset:data:geo:GSE146221 licence not read", "asset:data:geo:GSE17674 not downloaded", "asset:data:geo:GSE17674 licence not read", "asset:data:geo:GSE63156 not downloaded", "asset:data:geo:GSE63156 licence not read", "asset:data:geo:GSE68776 not downloaded", "asset:data:geo:GSE68776 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "cox_proportional_hazards", "label": "Survival analysis", "dsl_operations": ["cox_ph"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Univariate Cox regression (p < 0.06) was applied to generate the prognostic CRGs. Then LASSO algorithm with lambda.min was used to reduce variables [20]. Finally, CRGs signatures were screened out by multivariate step regression with the lowest Akaike information criterion (AIC) via \"survival\" package [21]."}}, {"id": "method-2", "family": "survival_analysis", "specific": "kaplan_meier", "label": "Survival analysis", "dsl_operations": ["survival_km"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.7, "band": "medium", "quote": "KM"}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "cox_ph", "expected_value": 0.0026, "unit": "p-value", "tolerance": null, "state": "complete", "note": "The threshold the paper applied to its own result, as the paper states it. A run that reproduces the effect is judged against this threshold."}], "gaps": []}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["cox_ph"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: cox_proportional_hazards."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE17674", "GSE63156", "GSE68776", "GSE146221"], "resolved_accessions": ["GSE17674", "GSE63156", "GSE68776", "GSE146221"], "statements": ["The data used in this study are available in publicly in GEO."], "basis": "The paper names GSE17674, GSE63156, GSE68776, GSE146221 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["cox_ph"], "assets": ["source:pmid:36871208", "data:geo:GSE146221"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE146221"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:32:36Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 15931, "completion_tokens": 2409, "cached_tokens": 256}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:36871208", "type": "paper", "label": "pmid:36871208"}, {"id": "source:pmid:36871208", "type": "manuscript", "label": "PMID 36871208 full text"}, {"id": "data:geo:GSE146221", "type": "dataset", "label": "GEO GSE146221"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:36871208", "type": "paper", "label": "pmid:36871208"}, {"id": "source:pmid:36871208", "type": "manuscript", "label": "PMID 36871208 full text"}, {"id": "data:geo:GSE146221", "type": "dataset", "label": "GEO GSE146221"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-36871208", "type": "extraction", "used": ["source:pmid:36871208"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE146221", "type": "accession_resolution", "used": ["data:geo:GSE146221"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:36871208", "parent_hash": "sha256:0bc0e72beb76ffe14464cddc438693cb9288507a1afd9bf8f5ff98dac0a1f7c6", "fork_of": null, "generation": 1}, "gaps": ["asset:data:geo:GSE146221 licence not read", "asset:data:geo:GSE146221 not downloaded", "asset:data:geo:GSE17674 licence not read", "asset:data:geo:GSE17674 not downloaded", "asset:data:geo:GSE63156 licence not read", "asset:data:geo:GSE63156 not downloaded", "asset:data:geo:GSE68776 licence not read", "asset:data:geo:GSE68776 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"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": ["Univariate Cox regression (p < 0.06) was applied to generate the prognostic CRGs. Then LASSO algorithm with lambda.min was used to reduce variables [20]. Finally, CRGs signatures were screened out by multivariate step regression with the lowest Akaike information criterion (AIC) via \"survival\" package [21]."], "order_basis": "analysis_only", "id": "assay:1"}]}