Development and Validation of a Robust Ferroptosis-Related Gene Panel for Breast Cancer Disease-Specific Survival.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34900981", "kind": "science-record", "revision": 4, "content_hash": "sha256:dec702c4a5bdcaaaa6bcce808183410c86e644a66c2c9846b416ab66d016c0cc", "created_at": "2026-11-01T17:36:37Z", "updated_at": "2026-11-01T22:05:22Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Development and Validation of a Robust Ferroptosis-Related Gene Panel for Breast Cancer Disease-Specific Survival.", "doi": "10.3389/fcell.2021.709180", "pmid": "34900981", "authors": ["Pei Li", "Benlong Yang", "Bingqiu Xiu", "Yayun Chi", "Jingyan Xue", "Jiong Wu"], "journal": "Frontiers in cell and developmental biology", "year": 2021, "abstract": "Background: New biomarker combinations have been increasingly developed to improve the precision of current diagnostic and therapeutic modalities. Recently, researchers have found that tumor cells are more vulnerable to ferroptosis. Furthermore, ferroptosis-related genes (FRG) are promising therapeutic targets in breast cancer patients. Therefore, this study aimed to identify FRG that could predict disease-specific survival (DSS) in breast cancer patients. Methods: Gene expression matrix and clinical data were downloaded from public databases. We included 960, 1,900, and 234 patients from the TCGA, METABRIC, and GSE3494 cohorts, respectively. Data for FRG were downloaded from the FerrDb website. Differential expression of FRG was analyzed by comparing the tumors with adjacent normal tissues. Univariate Cox analysis of DSS was performed to identify prognostic FRG. The TCGA-BRCA cohort was used to generate a nine-gene panel with the LASSO cox regression. The METABRIC and GSE3494 cohorts were used to validate the panel. The panel's median cut-off value was used to divide the patients into high- or low-risk subgroups. Analyses of immune microenvironment, functional pathways, and clinical correlation were conducted via GO and KEGG analyses to determine the differences between the two subgroups. Results: The DSS of the low-risk subgroup was longer than that of the high-risk subgroup. The panel's predictive ability was confirmed by ROC curves (TCGA cohort AUC values were 0.806, 0.695, and 0.669 for 2, 3, and 5 years respectively, and the METABRIC cohort AUC values were 0.706, 0.734, and 0.7, respectively for the same periods). The panel was an independent DSS prognostic indicator in the Cox regression analyses. (TCGA cohort: HR = 3.51, 95% CI = 1.792-6.875, p < 0.001; METABRIC cohort: HR = 1.76, 95% CI = 1.283-2.413, p < 0.001). Immune-related pathways were enriched in the high-risk subgroup. The two subgroups that were stratified by the nine-gene panel were also associated with histology type, tumor grade, TNM stage, and Her2-positive and TNBC subtypes. The patients in the high-risk subgroup, whose CTLA4 and PD-1 statuses were both positive or negative, demonstrated a substantial clinical benefit from combination therapy with anti-CTLA4 and anti-PD-1. Conclusion: The new gene panel consisting of nine FRG may be used to assess the prognosis and immune status of patients with breast cancer. A precise therapeutic approach can also be possible with risk stratification.", "claims": [{"id": "claim-method", "statement": "We conducted univariate and multivariate Cox analyses to test if the nine-gene panel was an independent predictor of DSS.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34900981", "locator": "sections[12] \"The Nine-Gene Panel has an Independent Prognostic Significance\" paragraph 2", "quote": "We conducted univariate and multivariate Cox analyses to test if the nine-gene panel was an independent predictor of DSS."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found here: https://portal.gdc.cancer.gov/repository http://www.cbioportal.org/study/summary?id=brca_metabric https://www.ncbi.nlm.nih.gov/gds/?term=GSE3494.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34900981", "locator": "sections[20] \"Data Availability Statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found here: https://portal.gdc.cancer.gov/repository http://www.cbioportal.org/study/summary?id=brca_metabric https://www.ncbi.nlm.nih.gov/gds/?term=GSE3494."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The panel was an independent DSS prognostic indicator in the Cox regression analyses.", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "The panel was an independent DSS prognostic indicator in the Cox regression analyses. (TCGA cohort: HR = 3.51, 95% CI = 1.792–6.875, p < 0.001; METABRIC cohort: HR = 1.76, 95% CI = 1.283–2.413, p < 0.001)."}, "evidence": [{"asset": "source:pmid:34900981", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The panel was an independent DSS prognostic indicator in the Cox regression analyses. (TCGA cohort: HR = 3.51, 95% CI = 1.792–6.875, p < 0.001; METABRIC cohort: HR = 1.76, 95% CI = 1.283–2.413, p < 0.001)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The panel was an independent DSS prognostic indicator in the Cox regression analyses.", "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:34900981"], "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:GSE3494"], "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:GSE3494"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34900981", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fcell.2021.709180", "sha256": "sha256:3a47160b247c6b94a12284ba85f9150888dec308e893e49cb3f50af5aed96e4c", "bytes": 52621, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fcell.2021.709180", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8655913", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE3494", "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=GSE3494", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE3494", "version": null, "note": "Publicly available datasets were analyzed in this study. 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The immunohistochemistry (IHC) of ferroptotic prognostic protein imag", "ctively, in the TCGA cohort (Figure 3D). The IHC staining results also provided the levels of", "for DSS (D, E, F). The immunohistochemistry (IHC) of ferroptotic prognostic protein images fr", "and adjcent normal tissues were shown by the IHC staining. Analysis of Nine FRG Genome Mutati"], "order_basis": "paper_text_order:5599", "id": "assay:1"}, {"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": ["We conducted univariate and multivariate Cox analyses to test if the nine-gene panel was an independent predictor of DSS."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}