Identification and Validation of an 11-Ferroptosis Related Gene Signature and Its Correlation With Immune Checkpoint Molecules in Glioma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34249910", "kind": "science-record", "revision": 8, "content_hash": "sha256:c50a101c84d4aa2b664dba88223f22573a97537419b5969110e3aacefc5e62cb", "created_at": "2026-11-01T15:41:42Z", "updated_at": "2026-11-01T22:47:03Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and Validation of an 11-Ferroptosis Related Gene Signature and Its Correlation With Immune Checkpoint Molecules in Glioma.", "doi": "10.3389/fcell.2021.652599", "pmid": "34249910", "authors": ["Zhuohui Chen", "Tong Wu", "Zhouyi Yan", "Mengqi Zhang"], "journal": "Frontiers in cell and developmental biology", "year": 2021, "abstract": "BACKGROUND: Glioma is the most common primary malignant brain tumor with significant mortality and morbidity. Ferroptosis, a novel form of programmed cell death (PCD), is critically involved in tumorigenesis, progression and metastatic processes.\nMETHODS: We revealed the relationship between ferroptosis-related genes and glioma by analyzing the mRNA expression profiles from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), GSE16011, and the Repository of Molecular Brain Neoplasia Data (REMBRANDT) datasets. The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was performed to construct a ferroptosis-associated gene signature in the TCGA cohort. Glioma patients from the CGGA, GSE16011, and REMBRANDT cohorts were used to validate the efficacy of the signature. Receiver operating characteristic (ROC) curve analysis was applied to measure the predictive performance of the risk score for overall survival (OS). Univariate and multivariate Cox regression analyses of the 11-gene signature were performed to determine whether the ability of the prognostic signature in predicting OS was independent. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to identify the potential biological functions and pathways of the signature. Subsequently, we performed single sample gene set enrichment analysis (ssGSEA) to explore the correlation between risk scores and immune status. Finally, seven putative small molecule drugs were predicted by Connectivity Map.\nRESULTS: The 11-gene signature was identified to divide patients into two risk groups. ROC curve analysis indicated the 11-gene signature as a potential diagnostic factor in glioma patients. Multivariate Cox regression analyses showed that the risk score was an independent predictive factor for overall survival. Functional analysis revealed that genes were enriched in iron-related molecular functions and immune-related biological processes. The results of ssGSEA indicated that the 11-gene signature was correlated with the initiation and progression of glioma. The small molecule drugs we selected showed significant potential to be used as putative drugs.\nCONCLUSION: we identified a novel ferroptosis-related gene signature for prognostic prediction in glioma patients and revealed the relationship between ferroptosis-related genes and immune checkpoint molecules.", "claims": [{"id": "claim-method", "statement": "Kaplan-Meier analysis was performed to compare the overall survival curves between different patient groups, with a log-rank test to evaluate the statistical significance.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34249910", "locator": "sections[10] \"Statistical Analysis\" paragraph 2", "quote": "Kaplan-Meier analysis was performed to compare the overall survival curves between different patient groups, with a log-rank test to evaluate the statistical significance."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found here: TCGA repository, https://portal.gdc.cancer.gov/; CGGA repository, http://www.cgga.org.cn/; GEO repository, https://www.ncbi.nlm.nih.gov/geo/; and GlioVis, http://gliovis.bioinfo.cnio.es/.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34249910", "locator": "sections[21] \"Data Availability Statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found here: TCGA repository, https://portal.gdc.cancer.gov/; CGGA repository, http://www.cgga.org.cn/; GEO repository, https://www.ncbi.nlm.nih.gov/geo/; and GlioVis, http://gliovis.bioinfo.cnio.es/."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "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:34249910"], "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:GSE16011"], "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:GSE16011"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34249910", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fcell.2021.652599", "sha256": "sha256:43d558643b4d938d902548919e5eed05d2a042684160a387697850c02b8bde0a", "bytes": 48084, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fcell.2021.652599", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8262596", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE16011", "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=GSE16011", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE16011", "version": null, "note": "Publicly available datasets were analyzed in this study. This data can be found here: TCGA repository, https://portal.gdc.cancer.gov/; CGGA repository, http://www.cgga.org.cn/; GEO repository, https://www.ncbi.nlm.nih.gov/geo/; and GlioVis, http://gliovis.bioinfo.cnio.es/.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. This data can be found here: TCGA repository, https://portal.gdc.cancer.gov/; CGGA repository, http://www.cgga.org.cn/; GEO repository, https://www.ncbi.nlm.nih.gov/geo/; and GlioVis, http://gliovis.bioinfo.cnio.es/.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM405200", "GSM405201", "GSM405202", "GSM405203", "GSM405204", "GSM405205", "GSM405206", "GSM405207", "GSM405208", "GSM405209", "GSM405210", "GSM405211", "GSM405212", "GSM405213", "GSM405214", "GSM405215", "GSM405216", "GSM405217", "GSM405218", "GSM405219", "GSM405220", "GSM405221", "GSM405222", "GSM405223", "GSM405224", "GSM405225", "GSM405226", "GSM405227", "GSM405228", "GSM405229", "GSM405230", "GSM405231", "GSM405232", "GSM405233", "GSM405234", "GSM405235", "GSM405236", "GSM405237", "GSM405238", "GSM405239", "GSM405240", "GSM405241", "GSM405242", "GSM405243", "GSM405244", "GSM405245", "GSM405246", "GSM405247", "GSM405248", "GSM405249", "GSM405250", "GSM405251", "GSM405252", "GSM405253", "GSM405254", "GSM405255", "GSM405256", "GSM405257", "GSM405258", "GSM405259", "GSM405260", "GSM405261", "GSM405262", "GSM405263", "GSM405264", "GSM405265", "GSM405266", "GSM405267", "GSM405268", "GSM405269", "GSM405270", "GSM405271", "GSM405272", "GSM405273", "GSM405274", "GSM405275", "GSM405276", "GSM405277", "GSM405278", "GSM405279", "GSM405280", "GSM405281", "GSM405282", "GSM405283", "GSM405284", "GSM405285", "GSM405286", "GSM405287", "GSM405288", "GSM405289", "GSM405290", "GSM405291", "GSM405292", "GSM405293", "GSM405294", "GSM405295", "GSM405296", "GSM405297", "GSM405298", "GSM405299", "GSM405300", "GSM405301", "GSM405302", "GSM405303", "GSM405304", "GSM405305", "GSM405306", "GSM405307", "GSM405308", "GSM405309", "GSM405310", "GSM405311", "GSM405312", "GSM405313", "GSM405314", "GSM405315", "GSM405316", "GSM405317", "GSM405318", "GSM405319", "GSM405320", "GSM405321", "GSM405322", "GSM405323", "GSM405324", "GSM405325", "GSM405326", "GSM405327", "GSM405328", "GSM405329", "GSM405330", "GSM405331", "GSM405332", "GSM405333", "GSM405334", "GSM405335", "GSM405336", "GSM405337", "GSM405338", "GSM405339", "GSM405340", "GSM405341", "GSM405342", "GSM405343", "GSM405344", "GSM405345", "GSM405346", "GSM405347", "GSM405348", "GSM405349", "GSM405350", "GSM405351", "GSM405352", "GSM405353", "GSM405354", "GSM405355", "GSM405356", "GSM405357", "GSM405358", "GSM405359", "GSM405360", "GSM405361", "GSM405362", "GSM405363", "GSM405364", "GSM405365", "GSM405366", "GSM405367", "GSM405368", "GSM405369", "GSM405370", "GSM405371", "GSM405372", "GSM405373", "GSM405374", "GSM405375", "GSM405376", "GSM405377", "GSM405378", "GSM405379", "GSM405380", "GSM405381", "GSM405382", "GSM405383", "GSM405384", "GSM405385", "GSM405386", "GSM405387", "GSM405388", "GSM405389", "GSM405390", "GSM405391", "GSM405392", "GSM405393", "GSM405394", "GSM405395", "GSM405396", "GSM405397", "GSM405398", "GSM405399", "GSM405400", "GSM405401", "GSM405402", "GSM405403", "GSM405404", "GSM405405", "GSM405406", "GSM405407", "GSM405408", "GSM405409", "GSM405410", "GSM405411", "GSM405412", "GSM405413", "GSM405414", "GSM405415", "GSM405416", "GSM405417", "GSM405418", "GSM405419", "GSM405420", "GSM405421", "GSM405422", "GSM405423", "GSM405424", "GSM405425", "GSM405426", "GSM405427", "GSM405428", "GSM405429", "GSM405430", "GSM405431", "GSM405432", "GSM405433", "GSM405434", "GSM405435", "GSM405436", "GSM405437", "GSM405438", "GSM405439", "GSM405440", "GSM405441", "GSM405442", "GSM405443", "GSM405444", "GSM405445", "GSM405446", "GSM405447", "GSM405448", "GSM405449", "GSM405450", "GSM405451", "GSM405452", "GSM405453", "GSM405454", "GSM405455", "GSM405456", "GSM405457", "GSM405458", "GSM405459", "GSM405460", "GSM405461", "GSM405462", "GSM405463", "GSM405464", "GSM405465", "GSM405466", "GSM405467", "GSM405468", "GSM405469", "GSM405470", "GSM405471", "GSM405472", "GSM405473", "GSM405474", "GSM405475", "GSM405476", "GSM405477", "GSM405478", "GSM405479", "GSM405480", "GSM405481", "GSM405482", "GSM405483"], "sample_count": 284, "group_sizes": null, "group_sizes_basis": null, "platform": "8542", "taxon": "Homo sapiens", "title": "Intrinsic Gene Expression Profiles of Gliomas are a Better Predictor of Survival than Histology", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:34249910:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:607a9342381fb264e02f2e16337162d3255ee93ff410c536c2641b6cb114132e", "bytes": 583, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#T1", "version": null, "note": "The calculated coefficient of the 11 ferroptosis-related genes.", "structure": {"pmcid": "PMC8262596", "section_index": 13, "section_title": "Construction of a Gene-Based Prognostic Model in the TCGA Cohort", "row_count": 12, "column_count": 2}, "table": {"label": "TABLE 1", "caption": "The calculated coefficient of the 11 ferroptosis-related genes.", "rows": [["Gene", "Coefficient"], ["AKR1C3", "–0.120098473470357"], ["ALOX12", "–0.0122009713910145"], ["CD44", "0.214177710154476"], ["FANCD2", "0.684183489406273"], ["CRYAB", "–0.104571744619555"], ["MT1G", "0.0523002991814781"], ["SAT1", "0.17208169582249"], ["HSBP1", "0.0301696571931318"], ["ZEB1", "–0.371498258625237"], ["FADS2", "–0.0378977482917486"], ["NFE2L2", "0.452805076174773"]], "row_count": 12, "column_count": 2, "numeric_cells": 13, "header_rows": 1, "locator": "section[13]/table-wrap[1]#T1"}}, {"id": "asset:table:pmid:34249910:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:d3002c8984b22b452e0a66b35e8f1da373cf45cac804dcd1f5d7ea05191f01fd", "bytes": 558, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[18]/table-wrap[1]#T2", "version": null, "note": "Drugs selected by CMap.", "structure": {"pmcid": "PMC8262596", "section_index": 18, "section_title": "Drug Screening Using the 11-Gene Signature With CMap and STITCH Database", "row_count": 8, "column_count": 5}, "table": {"label": "TABLE 2", "caption": "Drugs selected by CMap.", "rows": [["CMap name", "n", "Enrichment", "p", "Percent non-null"], ["Butacaine", "4", "–0.881", "0.00048", "100"], ["CAY-10397", "3", "–0.92", "0.00092", "100"], ["BAS-012416453", "3", "–0.886", "0.00288", "100"], ["PHA-00816795", "2", "–0.956", "0.00421", "100"], ["STOCK1N-35696", "2", "–0.884", "0.02696", "100"], ["Piperlongumine", "2", "–0.876", "0.03078", "100"], ["Sanguinarine", "2", "–0.871", "0.03306", "100"]], "row_count": 8, "column_count": 5, "numeric_cells": 32, "header_rows": 1, "locator": "section[18]/table-wrap[1]#T2"}}], "gaps": ["asset:data:geo:GSE16011 not downloaded", "asset:data:geo:GSE16011 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "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": 1.0, "band": "verbatim", "quote": "Kaplan-Meier analysis was performed to compare the overall survival curves between different patient groups, with a log-rank test to evaluate the statistical significance."}}, {"id": "method-2", "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": 0.7, "band": "medium", "quote": "Cox regression"}}, {"id": "method-3", "family": "survival_analysis", "specific": "log_rank_test", "label": "Survival analysis", "dsl_operations": ["logrank_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "log-rank"}}, {"id": "method-4", "family": "diagnostic_evaluation", "specific": "roc", "label": "Diagnostic test evaluation", "dsl_operations": ["confusion_counts", "roc_curve", "sensitivity_specificity", "solve_confusion_matrix", "classification_metrics", "published_precision_envelope"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["reference_standard_and_test"], "evidence": {"score": 0.7, "band": "medium", "quote": "ROC curve"}}], "targets": [], "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": ["survival_km"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: kaplan_meier."}, "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": ["GSE16011"], "resolved_accessions": ["GSE16011"], "statements": ["Publicly available datasets were analyzed in this study. This data can be found here: TCGA repository, https://portal.gdc.cancer.gov/; CGGA repository, http://www.cgga.org.cn/; GEO repository, https://www.ncbi.nlm.nih.gov/geo/; and GlioVis, http://gliovis.bioinfo.cnio.es/."], "basis": "The paper names GSE16011 in GEO repository and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["survival_km"], "assets": ["source:pmid:34249910", "data:geo:GSE16011", "asset:table:pmid:34249910:1", "asset:table:pmid:34249910:2"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE16011"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:32:17Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 35145, "completion_tokens": 2545, "cached_tokens": 23040}}, "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:34249910", "type": "paper", "label": "pmid:34249910"}, {"id": "source:pmid:34249910", "type": "manuscript", "label": "PMID 34249910 full text"}, {"id": "data:geo:GSE16011", "type": "dataset", "label": "GEO GSE16011"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34249910", "type": "paper", "label": "pmid:34249910"}, {"id": "source:pmid:34249910", "type": "manuscript", "label": "PMID 34249910 full text"}, {"id": "data:geo:GSE16011", "type": "dataset", "label": "GEO GSE16011"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34249910", "type": "extraction", "used": ["source:pmid:34249910"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE16011", "type": "accession_resolution", "used": ["data:geo:GSE16011"], "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:34249910", "parent_hash": "sha256:cb598e5354234eb904bd35149530bcb6dc4f8737f1226f1afdfa8ce1cd595544", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:GSE16011 licence not read", "asset:data:geo:GSE16011 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": ["survival_km"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Kaplan-Meier analysis was performed to compare the overall survival curves between different patient groups, with a log-rank test to evaluate the statistical significance."], "order_basis": "analysis_only", "id": "assay:1"}]}