Comprehensive Analysis of Ferroptosis-Related Markers for the Clinical and Biological Value in Gastric Cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34745421", "kind": "science-record", "revision": 3, "content_hash": "sha256:efd76bc72efa7450f05d317772fddfcd18770c96333f6ccf625f48fea818ec15", "created_at": "2026-11-01T17:36:26Z", "updated_at": "2026-11-01T21:26:34Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Comprehensive Analysis of Ferroptosis-Related Markers for the Clinical and Biological Value in Gastric Cancer.", "doi": "10.1155/2021/7007933", "pmid": "34745421", "authors": ["Yanfei Shao", "Hongtao Jia", "Shuchun Li", "Ling Huang", "Batuer Aikemu", "Guang Yang", "Sen Zhang", "Jing Sun", "Minhua Zheng"], "journal": "Oxidative medicine and cellular longevity", "year": 2021, "abstract": "Gastric cancer is a highly malignant tumor with poor survival rate. Ferroptosis, a newly defined regulated cell death, is closely related to several tumors. Introduction of ferroptosis is promising for cancer treatments. However, the predictive role of ferroptosis in GC remains elusive. In this study, we screened the ferroptosis-related genes which were differentially expressed between normal and GC tissues. Then, based on these differentially expressed genes (DEGs), the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regressions were applied to construct the 10-gene prognostic signature (SP1, MYB, ALDH3A2, KEAP1, AIFM2, ITGB4, TGFBR1, MAP1LC3B, NOX4, and ZFP36) in TCGA training dataset. Based on the median risk score, all GC patients in TCGA training dataset and GSE84437 testing dataset were classified into a high- or low-risk group. GC patients in the low-risk group showed significantly higher survival possibilities than those in the high-risk group (P < 0.001). Combined with the clinical characteristics, the risk score was proven as an independent factor for predicting the OS of GC patients. Besides, the GC patients in the high- or low-risk group showed significantly different GO and KEGG functional enrichments, somatic mutation, fractions of immune cells, and immunotherapy response. Then, the expression levels of these genes in signature were further verified in the GC cell lines and our own GC samples (30-paired tumor/normal tissues). Furthermore, the effects of ferroptosis inducer Erastin on these 10 ferroptosis-related genes in GC cell lines were also explored in our study. In conclusion, our study constructed a prognostic signature of 10 ferroptosis-related genes, which could well predict the prognosis and immunotherapy for GC patients.", "claims": [{"id": "claim-method", "statement": "In order to minimize the risk of overfitting, the least absolute shrinkage and selection operator (LASSO) regression was utilized to establish a gene prognostic signature and further screen the 10 potential hub genes from the FDEGs by the glmnet R package.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34745421", "locator": "sections[5] \"2.3. Establishment and Validation of a Prognostic Ferroptosis-Related Gene Signature\" paragraph 2", "quote": "In order to minimize the risk of overfitting, the least absolute shrinkage and selection operator (LASSO) regression was utilized to establish a gene prognostic signature and further screen the 10 potential hub genes from the FDEGs by the glmnet R package."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The RNA sequencing (RNA-seq) data and corresponding clinical characteristics and molecular information of gastric cancer samples in training cohort (TCGA-STAD) were downloaded from The Cancer Genome Atlas (TCGA) database by the “TCGAbiolinks” R package in February 2021. The RNA-seq data of normal human stomach samples in GTEx database was downloaded from the University of California Santa Cruz (UCSC, https://xenabrowser.net/datapages/). Besides, the gene expression data and corresponding clinical information of the external validation cohorts (GSE84437, GSE29272) were downloaded from the GEO database (https://www.ncbi.nlm.nih.gov/). Furthermore, the somatic mutation data of the TCGA-STAD was downloaded from the websites (https://portal.gdc.cancer.gov/). The 261 ferroptosis-related genes were downloaded from the FerrDb website (http://www.zhounan.org/ferrdb/), updating on 10 March 2021.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34745421", "locator": "sections[30] \"Data Availability\" paragraph 2", "quote": "The RNA sequencing (RNA-seq) data and corresponding clinical characteristics and molecular information of gastric cancer samples in training cohort (TCGA-STAD) were downloaded from The Cancer Genome Atlas (TCGA) database by the “TCGAbiolinks” R package in February 2021. The RNA-seq data of normal human stomach samples in GTEx database was downloaded from the University of California Santa Cruz (UCSC, https://xenabrowser.net/datapages/). Besides, the gene expression data and corresponding clinical information of the external validation cohorts (GSE84437, GSE29272) were downloaded from the GEO database (https://www.ncbi.nlm.nih.gov/). Furthermore, the somatic mutation data of the TCGA-STAD was downloaded from the websites (https://portal.gdc.cancer.gov/). The 261 ferroptosis-related genes were downloaded from the FerrDb website (http://www.zhounan.org/ferrdb/), updating on 10 March 2021."}], "state": "complete"}, {"id": "claim-target-result", "statement": "GC patients in the low-risk group showed significantly higher survival possibilities than those in the high-risk group (P < 0.001).", "kind": "quantitative", "target": {"value": 0.001, "unit": "p-value", "tolerance": null, "source": "GC patients in the low-risk group showed significantly higher survival possibilities than those in the high-risk group (P < 0.001)."}, "evidence": [{"asset": "source:pmid:34745421", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "GC patients in the low-risk group showed significantly higher survival possibilities than those in the high-risk group (P < 0.001)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "GC patients in the low-risk group showed significantly higher survival possibilities than those in the high-risk group (P < 0.001).", "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:34745421"], "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:GSE29272"], "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:GSE29272"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34745421", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1155/2021/7007933", "sha256": "sha256:400b0f0381cfb959922a982f2f68c508d833214c29797367d3c000ef95b77141", "bytes": 62886, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1155/2021/7007933", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8566081", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE29272", "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=GSE29272", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE29272", "version": null, "note": "The RNA sequencing (RNA-seq) data and corresponding clinical characteristics and molecular information of gastric cancer samples in training cohort (TCGA-STAD) were downloaded from The Cancer Genome Atlas (TCGA) database by the “TCGAbiolinks” R package in February 2021. The RNA-seq data of normal human stomach samples in GTEx database was downloaded from the University of California Santa Cruz (UCSC, https://xenabrowser.net/datapages/). Besides, the gene expression data and corresponding clinical information of the external validation cohorts (GSE84437, GSE29272) were downloaded from the GEO database (https://www.ncbi.nlm.nih.gov/). Furthermore, the somatic mutation data of the TCGA-STAD was downloaded from the websites (https://portal.gdc.cancer.gov/). The 261 ferroptosis-related genes were downloaded from the FerrDb website (http://www.zhounan.org/ferrdb/), updating on 10 March 2021.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The RNA sequencing (RNA-seq) data and corresponding clinical characteristics and molecular information of gastric cancer samples in training cohort (TCGA-STAD) were downloaded from The Cancer Genome Atlas (TCGA) database by the “TCGAbiolinks” R package in February 2021. The RNA-seq data of normal human stomach samples in GTEx database was downloaded from the University of California Santa Cruz (UCSC, https://xenabrowser.net/datapages/). Besides, the gene expression data and corresponding clinical information of the external validation cohorts (GSE84437, GSE29272) were downloaded from the GEO database (https://www.ncbi.nlm.nih.gov/). Furthermore, the somatic mutation data of the TCGA-STAD was downloaded from the websites (https://portal.gdc.cancer.gov/). 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The RNA-seq data of normal human stomach samples in GTEx database was downloaded from the University of California Santa Cruz (UCSC, https://xenabrowser.net/datapages/). Besides, the gene expression data and corresponding clinical information of the external validation cohorts (GSE84437, GSE29272) were downloaded from the GEO database (https://www.ncbi.nlm.nih.gov/). Furthermore, the somatic mutation data of the TCGA-STAD was downloaded from the websites (https://portal.gdc.cancer.gov/). The 261 ferroptosis-related genes were downloaded from the FerrDb website (http://www.zhounan.org/ferrdb/), updating on 10 March 2021.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The RNA sequencing (RNA-seq) data and corresponding clinical characteristics and molecular information of gastric cancer samples in training cohort (TCGA-STAD) were downloaded from The Cancer Genome Atlas (TCGA) database by the “TCGAbiolinks” R package in February 2021. The RNA-seq data of normal human stomach samples in GTEx database was downloaded from the University of California Santa Cruz (UCSC, https://xenabrowser.net/datapages/). Besides, the gene expression data and corresponding clinical information of the external validation cohorts (GSE84437, GSE29272) were downloaded from the GEO database (https://www.ncbi.nlm.nih.gov/). Furthermore, the somatic mutation data of the TCGA-STAD was downloaded from the websites (https://portal.gdc.cancer.gov/). 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"GSM4419533"], "sample_count": 483, "group_sizes": null, "group_sizes_basis": null, "platform": "6947", "taxon": "Homo sapiens", "title": "Molecular subtypes in gastric 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:GSE29272 not downloaded", "asset:data:geo:GSE29272 licence not read", "asset:data:geo:GSE84437 not downloaded", "asset:data:geo:GSE84437 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": "In order to minimize the risk of overfitting, the least absolute shrinkage and selection operator (LASSO) regression was utilized to establish a gene prognostic signature and further screen the 10 potential hub genes from the FDEGs by the glmnet R package."}}, {"id": "method-2", "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-3", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.8, "band": "high", "quote": "GO enrichment"}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "cox_ph", "expected_value": 0.001, "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": ["GSE84437", "GSE29272"], "resolved_accessions": ["GSE84437", "GSE29272"], "statements": ["The RNA sequencing (RNA-seq) data and corresponding clinical characteristics and molecular information of gastric cancer samples in training cohort (TCGA-STAD) were downloaded from The Cancer Genome Atlas (TCGA) database by the “TCGAbiolinks” R package in February 2021. The RNA-seq data of normal human stomach samples in GTEx database was downloaded from the University of California Santa Cruz (UCSC, https://xenabrowser.net/datapages/). Besides, the gene expression data and corresponding clinical information of the external validation cohorts (GSE84437, GSE29272) were downloaded from the GEO database (https://www.ncbi.nlm.nih.gov/). Furthermore, the somatic mutation data of the TCGA-STAD was downloaded from the websites (https://portal.gdc.cancer.gov/). The 261 ferroptosis-related genes were downloaded from the FerrDb website (http://www.zhounan.org/ferrdb/), updating on 10 March 2021."], "basis": "The paper names GSE84437, GSE29272 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:34745421", "data:geo:GSE29272"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE29272"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:06:23Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 18569, "completion_tokens": 2167, "cached_tokens": 128}}, "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:34745421", "type": "paper", "label": "pmid:34745421"}, {"id": "source:pmid:34745421", "type": "manuscript", "label": "PMID 34745421 full text"}, {"id": "data:geo:GSE29272", "type": "dataset", "label": "GEO GSE29272"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34745421", "type": "paper", "label": "pmid:34745421"}, {"id": "source:pmid:34745421", "type": "manuscript", "label": "PMID 34745421 full text"}, {"id": "data:geo:GSE29272", "type": "dataset", "label": "GEO GSE29272"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34745421", "type": "extraction", "used": ["source:pmid:34745421"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE29272", "type": "accession_resolution", "used": ["data:geo:GSE29272"], "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:34745421", "parent_hash": "sha256:4d6cfbf61d1a179be7b65f31f3b6ac2931a6132c40982136d66a26b12f90f8a1", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE29272 licence not read", "asset:data:geo:GSE29272 not downloaded", "asset:data:geo:GSE84437 licence not read", "asset:data:geo:GSE84437 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["nstitute of Digestive Surgery. All the three cell lines were cultured in RPMI-1640 medium (Meilunbio, China) suppl", "stive Surgery. All the three cell lines were cultured in RPMI-1640 medium (Meilunbio, China) suppleme"], "order_basis": "paper_text_order:2130", "id": "assay:1"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["MGC-803 cell lines were all investigated by real-time PCR. The results indicated that the mRNA express", "03 after being treated with 10 μM Erastin by real-time PCR. (i) The plot detects the different protein"], "order_basis": "paper_text_order:9690", "id": "assay:2"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["P1, NOX4, and SP1) were further confirmed by western blot except AIFM2 and SP1 in the HGC-27 cell line", "03 after being treated with 10 μM Erastin by western blot. ∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001, and ∗∗"], "order_basis": "paper_text_order:10320", "id": "assay:3"}, {"role": "data_generation", "definition_id": "flow_cytometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["MGC-803 cell lines treated with Erastin. The flow cytometry and fluorescence microscope plots verify the"], "order_basis": "paper_text_order:10629", "id": "assay:4"}, {"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": ["In order to minimize the risk of overfitting, the least absolute shrinkage and selection operator (LASSO) regression was utilized to establish a gene prognostic signature and further screen the 10 potential hub genes from the FDEGs by the glmnet R package."], "order_basis": "consumes_earlier_output", "id": "assay:5"}]}