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pmid:36245988

Prognostic Modeling of Lung Adenocarcinoma Based on Hypoxia and Ferroptosis-Related Genes.

Chang Liu · Yan-Qin Ruan · Lai-Hao Qu · Zhen-Hua Li · Chao Xie · Ya-Qiang Pan · Hao-Fei Li · Ding-Biao Li

Journal of oncology · 2022 doi:10.1155/2022/1022580

Paper

complete

Experiment

complete

Data

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Analysis

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Execution

absent

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title
Prognostic Modeling of Lung Adenocarcinoma Based on Hypoxia and Ferroptosis-Related Genes.
doi
10.1155/2022/1022580
pmid
36245988
authors array · 8 items
[0]
Chang Liu
[1]
Yan-Qin Ruan
[2]
Lai-Hao Qu
[3]
Zhen-Hua Li
[4]
Chao Xie
[5]
Ya-Qiang Pan
[6]
Hao-Fei Li
[7]
Ding-Biao Li
journal
Journal of oncology
year
2022
abstract
Background: It is well known that hypoxia and ferroptosis are intimately connected with tumor development. The purpose of this investigation was to identify whether they have a prognostic signature. To this end, genes related to hypoxia and ferroptosis scores were investigated using bioinformatics analysis to stratify the risk of lung adenocarcinoma. Methods: Hypoxia and ferroptosis scores were estimated using The Cancer Genome Atlas (TCGA) database-derived cohort transcriptome profiles via the single sample gene set enrichment analysis (ssGSEA) algorithm. The candidate genes associated with hypoxia and ferroptosis scores were identified using weighted correlation network analysis (WGCNA) and differential expression analysis. The prognostic genes in this study were discovered using the Cox regression (CR) model in conjunction with the LASSO method, which was then utilized to create a prognostic signature. The efficacy, accuracy, and clinical value of the prognostic model were evaluated using an independent validation cohort, Receiver Operator Characteristic (ROC) curve, and nomogram. The analysis of function and immune cell infiltration was also carried out. Results: Here, we appraised 152 candidate genes expressed not the same, which were related to hypoxia and ferroptosis for prognostic modeling in The Cancer Genome Atlas Lung Adenocarcinoma (TCGA-LUAD) cohort, and these genes were further validated in the GSE31210 cohort. We found that the 14-gene-based prognostic model, utilizing MAPK4, TNS4, WFDC2, FSTL3, ITGA2, KLK11, PHLDB2, VGLL3, SNX30, KCNQ3, SMAD9, ANGPTL4, LAMA3, and STK32A, performed well in predicting the prognosis in lung adenocarcinoma. ROC and nomogram analyses showed that risk scores based on prognostic signatures provided desirable predictive accuracy and clinical utility. Moreover, gene set variance analysis showed differential enrichment of 33 hallmark gene sets between different risk groups. Additionally, our results indicated that a higher risk score will lead to more fibroblasts and activated CD4 T cells but fewer myeloid dendritic cells, endothelial cells, eosinophils, immature dendritic cells, and neutrophils. Conclusion: Our research found a 14-gene signature and established a nomogram that accurately predicted the prognosis in patients with lung adenocarcinoma. Clinical decision-making and therapeutic customization may benefit from these results, which may serve as a valuable reference in the future.
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The prognostic genes in this study were discovered using the Cox regression (CR) model in conjunction with the LASSO method, which was then utilized to create a prognostic signature.
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The prognostic genes in this study were discovered using the Cox regression (CR) model in conjunction with the LASSO method, which was then utilized to create a prognostic signature.
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We found that the 14-gene-based prognostic model, utilizing MAPK4, TNS4, WFDC2, FSTL3, ITGA2, KLK11, PHLDB2, VGLL3, SNX30, KCNQ3, SMAD9, ANGPTL4, LAMA3, and STK32A, performed well in predicting the prognosis in lung adenocarcinoma.
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We found that the 14-gene-based prognostic model, utilizing MAPK4, TNS4, WFDC2, FSTL3, ITGA2, KLK11, PHLDB2, VGLL3, SNX30, KCNQ3, SMAD9, ANGPTL4, LAMA3, and STK32A, performed well in predicting the prognosis in lung adenocarcinoma.
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We found that the 14-gene-based prognostic model, utilizing MAPK4, TNS4, WFDC2, FSTL3, ITGA2, KLK11, PHLDB2, VGLL3, SNX30, KCNQ3, SMAD9, ANGPTL4, LAMA3, and STK32A, performed well in predicting the prognosis in lung adenocarcinoma.
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ba34b49490d9bfaf
lineage object · 4 fields
parent_id
pmid:36245988
parent_hash
sha256:afa1a059a91e4489be14cb1c611f2a887521527f014b8a988e5f3e2f6dd9b8c0
fork_of
null
gaps array · 7 items
[0]
asset:data:geo:GSE31210 licence not read
[1]
asset:data:geo:GSE31210 not downloaded
[2]
execution.not_run
[3]
method.reader_differs_from_extractor
[4]
review.human_critique
[5]
review.independent_reader
[6]
review.machine_critique
assays array · 1 item
[0] object · 11 fields
role
analysis
definition_id
survival_analysis
definition_version
f2132e96ae6c7a4e
required_operations array · 1 item
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cox_ph
support_state
supported
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
The prognostic genes in this study were discovered using the Cox regression (CR) model in conjunction with the LASSO method, which was then utilized to create a prognostic signature.
order_basis
analysis_only
id
assay:1
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36245988", "kind": "science-record", "revision": 4, "content_hash": "sha256:21ff53750cc9867384a164bc24bda4100227ef279ac1e100bba75dd70277f61e", "created_at": "2026-11-01T18:15:37Z", "updated_at": "2026-11-01T22:07:51Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Prognostic Modeling of Lung Adenocarcinoma Based on Hypoxia and Ferroptosis-Related Genes.", "doi": "10.1155/2022/1022580", "pmid": "36245988", "authors": ["Chang Liu", "Yan-Qin Ruan", "Lai-Hao Qu", "Zhen-Hua Li", "Chao Xie", "Ya-Qiang Pan", "Hao-Fei Li", "Ding-Biao Li"], "journal": "Journal of oncology", "year": 2022, "abstract": "Background: It is well known that hypoxia and ferroptosis are intimately connected with tumor development. The purpose of this investigation was to identify whether they have a prognostic signature. To this end, genes related to hypoxia and ferroptosis scores were investigated using bioinformatics analysis to stratify the risk of lung adenocarcinoma.\nMethods: Hypoxia and ferroptosis scores were estimated using The Cancer Genome Atlas (TCGA) database-derived cohort transcriptome profiles via the single sample gene set enrichment analysis (ssGSEA) algorithm. The candidate genes associated with hypoxia and ferroptosis scores were identified using weighted correlation network analysis (WGCNA) and differential expression analysis. The prognostic genes in this study were discovered using the Cox regression (CR) model in conjunction with the LASSO method, which was then utilized to create a prognostic signature. The efficacy, accuracy, and clinical value of the prognostic model were evaluated using an independent validation cohort, Receiver Operator Characteristic (ROC) curve, and nomogram. The analysis of function and immune cell infiltration was also carried out.\nResults: Here, we appraised 152 candidate genes expressed not the same, which were related to hypoxia and ferroptosis for prognostic modeling in The Cancer Genome Atlas Lung Adenocarcinoma (TCGA-LUAD) cohort, and these genes were further validated in the GSE31210 cohort. We found that the 14-gene-based prognostic model, utilizing MAPK4, TNS4, WFDC2, FSTL3, ITGA2, KLK11, PHLDB2, VGLL3, SNX30, KCNQ3, SMAD9, ANGPTL4, LAMA3, and STK32A, performed well in predicting the prognosis in lung adenocarcinoma. ROC and nomogram analyses showed that risk scores based on prognostic signatures provided desirable predictive accuracy and clinical utility. Moreover, gene set variance analysis showed differential enrichment of 33 hallmark gene sets between different risk groups. Additionally, our results indicated that a higher risk score will lead to more fibroblasts and activated CD4 T cells but fewer myeloid dendritic cells, endothelial cells, eosinophils, immature dendritic cells, and neutrophils.\nConclusion: Our research found a 14-gene signature and established a nomogram that accurately predicted the prognosis in patients with lung adenocarcinoma. Clinical decision-making and therapeutic customization may benefit from these results, which may serve as a valuable reference in the future.", "claims": [{"id": "claim-method", "statement": "The prognostic genes in this study were discovered using the Cox regression (CR) model in conjunction with the LASSO method, which was then utilized to create a prognostic signature.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36245988", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "The prognostic genes in this study were discovered using the Cox regression (CR) model in conjunction with the LASSO method, which was then utilized to create a prognostic signature."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36245988", "locator": "sections[31] \"Data Availability\" paragraph 2", "quote": "The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "We found that the 14-gene-based prognostic model, utilizing MAPK4, TNS4, WFDC2, FSTL3, ITGA2, KLK11, PHLDB2, VGLL3, SNX30, KCNQ3, SMAD9, ANGPTL4, LAMA3, and STK32A, performed well in predicting the prognosis in lung adenocarcinoma.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36245988", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "We found that the 14-gene-based prognostic model, utilizing MAPK4, TNS4, WFDC2, FSTL3, ITGA2, KLK11, PHLDB2, VGLL3, SNX30, KCNQ3, SMAD9, ANGPTL4, LAMA3, and STK32A, performed well in predicting the prognosis in lung adenocarcinoma."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "We found that the 14-gene-based prognostic model, utilizing MAPK4, TNS4, WFDC2, FSTL3, ITGA2, KLK11, PHLDB2, VGLL3, SNX30, KCNQ3, SMAD9, ANGPTL4, LAMA3, and STK32A, performed well in predicting the prognosis in lung adenocarcinoma.", "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:36245988"], "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:GSE31210"], "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:GSE31210"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36245988", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1155/2022/1022580", "sha256": "sha256:8f40ed0a238498a7a2118bd4b1325b7fb7e0a23847ff84a0353a1e90dd158a2b", "bytes": 67765, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1155/2022/1022580", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9553523", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE31210", "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=GSE31210", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE31210", "version": null, "note": "The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.", 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"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 prognostic genes in this study were discovered using the Cox regression (CR) model in conjunction with the LASSO method, which was then utilized to create a prognostic signature."}}, {"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": 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE31210"], "resolved_accessions": ["GSE31210"], "statements": ["The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request."], "basis": "The paper names GSE31210 in Gene Expression Omnibus (GEO) database 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:36245988", "data:geo:GSE31210"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE31210"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:11:06Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 20095, "completion_tokens": 1408, "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:36245988", "type": "paper", "label": "pmid:36245988"}, {"id": "source:pmid:36245988", "type": "manuscript", "label": "PMID 36245988 full text"}, {"id": "data:geo:GSE31210", "type": "dataset", "label": "GEO GSE31210"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:36245988", "type": "paper", "label": "pmid:36245988"}, {"id": "source:pmid:36245988", "type": "manuscript", "label": "PMID 36245988 full text"}, {"id": "data:geo:GSE31210", "type": "dataset", "label": "GEO GSE31210"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-36245988", "type": "extraction", "used": ["source:pmid:36245988"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE31210", "type": "accession_resolution", "used": ["data:geo:GSE31210"], "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:36245988", "parent_hash": "sha256:afa1a059a91e4489be14cb1c611f2a887521527f014b8a988e5f3e2f6dd9b8c0", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE31210 licence not read", "asset:data:geo:GSE31210 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 prognostic genes in this study were discovered using the Cox regression (CR) model in conjunction with the LASSO method, which was then utilized to create a prognostic signature."], "order_basis": "analysis_only", "id": "assay:1"}]}