A Novel Ferroptosis-Related Gene Signature to Predict Prognosis in Patients with Head and Neck Squamous Cell Carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34853622", "kind": "science-record", "revision": 4, "content_hash": "sha256:db4ca0395a51e9526929be330af97695dec2683b60915359854e47e3235f5813", "created_at": "2026-11-01T17:36:33Z", "updated_at": "2026-11-01T22:05:16Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A Novel Ferroptosis-Related Gene Signature to Predict Prognosis in Patients with Head and Neck Squamous Cell Carcinoma.", "doi": "10.1155/2021/5759927", "pmid": "34853622", "authors": ["Li Xu", "Ying-Ying Li", "Yang-Chun Zhang", "Yong-Xu Wu", "Dan-Dan Guo", "Dan Long", "Zhao-Hui Liu"], "journal": "Disease markers", "year": 2021, "abstract": "The clinical TNM staging system is currently used to evaluate the prognosis of head and neck squamous cell carcinoma (HNSCC). The 5-year survival rate for patients with HNSCC is less than 50%, which is attributed to the lack of reliable prognostic biomarkers. Ferroptosis-related genes (FRGs) regulate cancer initiation and progression. Therefore, we analyzed the correlation between FRGs and the clinical outcomes of patients with HNSCC. A typical prognostic model of FRGs for HNSCC was constructed using bioinformatics tools and data from public databases, including The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and GeneCards. The model was generated based on the following six FRGs: ATG5, PRDX6, OTUB1, FTH1, SOCS1, and MAP3K5. The accuracy of model prediction was analyzed systematically. The overall survival (OS) of the high-risk group was significantly lower than that of the low-risk group. The AUC for 1-year, 3-year, and 5-year survival were 0.645, 0.721, and 0.737, respectively, in the training set (TCGA cohort) and 0.726, 0.620, and 0.584, respectively, in the validation set (GSE65858). The multivariate Cox regression analysis revealed that the risk score was an independent prognostic factor for HNSCC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that six FRGs were enriched in the ferroptosis pathway. A novel FRG prognostic signature model was established for HNSCC. The findings of this study reveal that FRGs are potential biomarkers for HNSCC.", "claims": [{"id": "claim-method", "statement": "The multivariate Cox regression analysis revealed that the risk score was an independent prognostic factor for HNSCC.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34853622", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "The multivariate Cox regression analysis revealed that the risk score was an independent prognostic factor for HNSCC."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data that support the findings of this study are available from the corresponding author upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34853622", "locator": "sections[21] \"Data Availability\" paragraph 2", "quote": "The data that support the findings of this study are available from the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The AUC for 1-year, 3-year, and 5-year survival were 0.645, 0.721, and 0.737, respectively, in the training set (TCGA cohort) and 0.726, 0.620, and 0.584, respectively, in the validation set (GSE65858).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:34853622", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "The AUC for 1-year, 3-year, and 5-year survival were 0.645, 0.721, and 0.737, respectively, in the training set (TCGA cohort) and 0.726, 0.620, and 0.584, respectively, in the validation set (GSE65858)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The AUC for 1-year, 3-year, and 5-year survival were 0.645, 0.721, and 0.737, respectively, in the training set (TCGA cohort) and 0.726, 0.620, and 0.584, respectively, in the validation set (GSE65858).", "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:34853622"], "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:GSE65858"], "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:GSE65858"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34853622", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1155/2021/5759927", "sha256": "sha256:fe8acdade5b60bbc32e19d1390a7ee2a3dc6d2a9bc7d06eed91c72ebf95aee2d", "bytes": 43927, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1155/2021/5759927", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8629675", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE65858", "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=GSE65858", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE65858", "version": null, "note": "The data that support the findings of this study are available from the corresponding author upon reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data that support the findings of this study are available from the corresponding author upon reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1607684", "GSM1607685", "GSM1607686", "GSM1607687", "GSM1607688", "GSM1607689", "GSM1607690", "GSM1607691", "GSM1607692", "GSM1607693", "GSM1607694", "GSM1607695", "GSM1607696", "GSM1607697", "GSM1607698", "GSM1607699", "GSM1607700", "GSM1607701", "GSM1607702", "GSM1607703", "GSM1607704", "GSM1607705", "GSM1607706", "GSM1607707", "GSM1607708", "GSM1607709", "GSM1607710", "GSM1607711", "GSM1607712", "GSM1607713", "GSM1607714", "GSM1607715", "GSM1607716", "GSM1607717", "GSM1607718", "GSM1607719", "GSM1607720", "GSM1607721", "GSM1607722", "GSM1607723", "GSM1607724", "GSM1607725", "GSM1607726", "GSM1607727", "GSM1607728", "GSM1607729", "GSM1607730", "GSM1607731", "GSM1607732", "GSM1607733", "GSM1607734", "GSM1607735", "GSM1607736", "GSM1607737", "GSM1607738", "GSM1607739", "GSM1607740", "GSM1607741", "GSM1607742", "GSM1607743", "GSM1607744", "GSM1607745", "GSM1607746", "GSM1607747", "GSM1607748", "GSM1607749", "GSM1607750", "GSM1607751", "GSM1607752", "GSM1607753", "GSM1607754", "GSM1607755", "GSM1607756", "GSM1607757", "GSM1607758", "GSM1607759", "GSM1607760", "GSM1607761", "GSM1607762", "GSM1607763", "GSM1607764", "GSM1607765", "GSM1607766", "GSM1607767", "GSM1607768", "GSM1607769", "GSM1607770", "GSM1607771", "GSM1607772", "GSM1607773", "GSM1607774", "GSM1607775", "GSM1607776", "GSM1607777", "GSM1607778", "GSM1607779", "GSM1607780", "GSM1607781", "GSM1607782", "GSM1607783", "GSM1607784", "GSM1607785", "GSM1607786", "GSM1607787", "GSM1607788", "GSM1607789", "GSM1607790", "GSM1607791", "GSM1607792", "GSM1607793", "GSM1607794", "GSM1607795", "GSM1607796", "GSM1607797", "GSM1607798", "GSM1607799", "GSM1607800", "GSM1607801", "GSM1607802", "GSM1607803", "GSM1607804", "GSM1607805", "GSM1607806", "GSM1607807", "GSM1607808", "GSM1607809", "GSM1607810", "GSM1607811", "GSM1607812", "GSM1607813", "GSM1607814", "GSM1607815", "GSM1607816", "GSM1607817", "GSM1607818", "GSM1607819", "GSM1607820", "GSM1607821", "GSM1607822", "GSM1607823", "GSM1607824", "GSM1607825", "GSM1607826", "GSM1607827", "GSM1607828", "GSM1607829", "GSM1607830", "GSM1607831", "GSM1607832", "GSM1607833", "GSM1607834", "GSM1607835", "GSM1607836", "GSM1607837", "GSM1607838", "GSM1607839", "GSM1607840", "GSM1607841", "GSM1607842", "GSM1607843", "GSM1607844", "GSM1607845", "GSM1607846", "GSM1607847", "GSM1607848", "GSM1607849", "GSM1607850", "GSM1607851", "GSM1607852", "GSM1607853", "GSM1607854", "GSM1607855", "GSM1607856", "GSM1607857", "GSM1607858", "GSM1607859", "GSM1607860", "GSM1607861", "GSM1607862", "GSM1607863", "GSM1607864", "GSM1607865", "GSM1607866", "GSM1607867", "GSM1607868", "GSM1607869", "GSM1607870", "GSM1607871", "GSM1607872", "GSM1607873", "GSM1607874", "GSM1607875", "GSM1607876", "GSM1607877", "GSM1607878", "GSM1607879", "GSM1607880", "GSM1607881", "GSM1607882", "GSM1607883", "GSM1607884", "GSM1607885", "GSM1607886", "GSM1607887", "GSM1607888", "GSM1607889", "GSM1607890", "GSM1607891", "GSM1607892", "GSM1607893", "GSM1607894", "GSM1607895", "GSM1607896", "GSM1607897", "GSM1607898", "GSM1607899", "GSM1607900", "GSM1607901", "GSM1607902", "GSM1607903", "GSM1607904", "GSM1607905", "GSM1607906", "GSM1607907", "GSM1607908", "GSM1607909", "GSM1607910", "GSM1607911", "GSM1607912", "GSM1607913", "GSM1607914", "GSM1607915", "GSM1607916", "GSM1607917", "GSM1607918", "GSM1607919", "GSM1607920", "GSM1607921", "GSM1607922", "GSM1607923", "GSM1607924", "GSM1607925", "GSM1607926", "GSM1607927", "GSM1607928", "GSM1607929", "GSM1607930", "GSM1607931", "GSM1607932", "GSM1607933", "GSM1607934", "GSM1607935", "GSM1607936", "GSM1607937", "GSM1607938", "GSM1607939", "GSM1607940", "GSM1607941", "GSM1607942", "GSM1607943", "GSM1607944", "GSM1607945", "GSM1607946", "GSM1607947", "GSM1607948", "GSM1607949", "GSM1607950", "GSM1607951", "GSM1607952", "GSM1607953"], "sample_count": 270, "group_sizes": null, "group_sizes_basis": null, "platform": "10558", "taxon": "Homo sapiens", "title": "Gene expression patterns and TP53 mutations are associated with HPV RNA status, lymph node metastasis, and survival in head and neck cancer", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE65858 not downloaded", "asset:data:geo:GSE65858 licence not read"]}, "analysis": {"state": "partial", "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": "The multivariate Cox regression analysis revealed that the risk score was an independent prognostic factor for HNSCC."}}, {"id": "method-2", "family": "group_comparison", "specific": "wilcoxon", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Wilcoxon"}}, {"id": "method-3", "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": 0.8, "band": "high", "quote": "Kaplan-Meier"}}, {"id": "method-4", "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-5", "family": "principal_component_analysis", "specific": "pca", "label": "Principal component analysis", "dsl_operations": ["pca_fit"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["wide_numeric_matrix"], "evidence": {"score": 0.8, "band": "high", "quote": "PCA"}}, {"id": "method-6", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.8, "band": "high", "quote": "PPI"}}, {"id": "method-7", "family": "model_calibration", "specific": "decision_curve", "label": "Model calibration / clinical utility", "dsl_operations": ["calibration_bins", "net_benefit"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["predictions_and_outcomes"], "evidence": {"score": 0.8, "band": "high", "quote": "decision curve analysis"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor"]}, "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": ["GSE65858"], "resolved_accessions": ["GSE65858"], "statements": ["The data that support the findings of this study are available from the corresponding author upon reasonable request."], "basis": "The paper names GSE65858 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:34853622", "data:geo:GSE65858"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE65858"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:09:27Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 13840, "completion_tokens": 1387, "cached_tokens": 264}}, "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:34853622", "type": "paper", "label": "pmid:34853622"}, {"id": "source:pmid:34853622", "type": "manuscript", "label": "PMID 34853622 full text"}, {"id": "data:geo:GSE65858", "type": "dataset", "label": "GEO GSE65858"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34853622", "type": "paper", "label": "pmid:34853622"}, {"id": "source:pmid:34853622", "type": "manuscript", "label": "PMID 34853622 full text"}, {"id": "data:geo:GSE65858", "type": "dataset", "label": "GEO GSE65858"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34853622", "type": "extraction", "used": ["source:pmid:34853622"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE65858", "type": "accession_resolution", "used": ["data:geo:GSE65858"], "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:34853622", "parent_hash": "sha256:b69e5652f29afb099a63bde7fcfef4ac5f7bc4ec1e417825655d4da263921c95", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE65858 licence not read", "asset:data:geo:GSE65858 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "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": ["The multivariate Cox regression analysis revealed that the risk score was an independent prognostic factor for HNSCC."], "order_basis": "analysis_only", "id": "assay:1"}]}