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pmid:35844488

Diagnostic and Predictive Values of Ferroptosis-Related Genes in Child Sepsis.

Zhi Li · Chi Zhang · Yiqi Liu · Fang Wang · Baoling Zhao · Junmei Yang · Yongjing Zhao · Hong Zhao · Guiqiang Wang

Frontiers in immunology · 2022 doi:10.3389/fimmu.2022.881914

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Experiment

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Data

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pmid:35844488
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science-record
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title
Diagnostic and Predictive Values of Ferroptosis-Related Genes in Child Sepsis.
doi
10.3389/fimmu.2022.881914
pmid
35844488
authors array · 9 items
[0]
Zhi Li
[1]
Chi Zhang
[2]
Yiqi Liu
[3]
Fang Wang
[4]
Baoling Zhao
[5]
Junmei Yang
[6]
Yongjing Zhao
[7]
Hong Zhao
[8]
Guiqiang Wang
journal
Frontiers in immunology
year
2022
abstract
Background: Early diagnosis of sepsis in children was essential to reducing mortality. This study aimed to explore the value of ferroptosis-related genes in children with sepsis. Methods: We screened the septic children microarray dataset from the GEO database and analyzed the ferroptosis-related differentially expressed genes (DEGs). A functional analysis of ferroptosis-related DEGs was performed. The protein-protein interaction network was used to identify hub genes. We explored the immune landscape of sepsis and controls. The value of hub genes in diagnosing sepsis was tested in the training (GSE26440) and validation sets (GSE13904), and ELISA was used to verify their diagnostic value in children with sepsis in our hospital. Results: A total of 2,103 DEGs in GSE26440 were obtained, of which ferroptosis-related DEGs were 34. Enrichment analysis showed significant enrichment in the ferroptosis and hypoxia pathways (i.e., HIF-1 pathway). The top three genes (HMOX1, MAPK14, TLR4) were selected as hub genes. Immunological analysis suggested that 10 cell types (i.e., CD8/CD4 T cells) were lower in sepsis. Immune checkpoint-related genes CD274 (PD-L1), HAVCR2 (TIM3), and SIGLEC15 were overexpressed in sepsis. The AUROC for the diagnosis of sepsis for HMOX1 and TLR4 ranged from 0.77 to 0.81, while the AUROC of MAPK14 reached 0.935 and 0.941 in the training and validation sets. Serum ELISA results of HMOX1 and TLR4 showed no significant difference in differentiating sepsis. The AUROC of MAPK14 was 0.877. When the diagnostic threshold was 74.852 ng/ml, the sensitivity and specificity were 0.906 and 0.719, respectively. Conclusion: Ferroptosis-related gene MAPK14 is of considerable value in the early diagnosis of sepsis in children.
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The diagnostic accuracy of three hub genes was analyzed with receiver operating characteristic curves (ROC) and expressed as the area under the ROC curves (AUROC) and 95% CI.
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The diagnostic accuracy of three hub genes was analyzed with receiver operating characteristic curves (ROC) and expressed as the area under the ROC curves (AUROC) and 95% CI.
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sections[20] "Data Availability Statement" paragraph 2
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The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/supplementary material.
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MAPK14 was the ferroptosis-related hub gene with substantial diagnostic value for early diagnosis of sepsis in children.
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Ferroptosis-related gene MAPK14 is of considerable value in the early diagnosis of sepsis in children.
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MAPK14 was the ferroptosis-related hub gene with substantial diagnostic value for early diagnosis of sepsis in children.
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title
Expression profiling across the pediatric systemic inflammatory response syndrome, sepsis, and septic shock spectrum
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Expression data for derivation of septic shock subgroups
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The diagnostic accuracy of three hub genes was analyzed with receiver operating characteristic curves (ROC) and expressed as the area under the ROC curves (AUROC) and 95% CI.
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35844488", "kind": "science-record", "revision": 4, "content_hash": "sha256:e6d0c609ceca29527eb90319129bb4cb629fe0508de9ec1697740edaa5c90ece", "created_at": "2026-11-01T18:14:54Z", "updated_at": "2026-11-01T22:07:02Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Diagnostic and Predictive Values of Ferroptosis-Related Genes in Child Sepsis.", "doi": "10.3389/fimmu.2022.881914", "pmid": "35844488", "authors": ["Zhi Li", "Chi Zhang", "Yiqi Liu", "Fang Wang", "Baoling Zhao", "Junmei Yang", "Yongjing Zhao", "Hong Zhao", "Guiqiang Wang"], "journal": "Frontiers in immunology", "year": 2022, "abstract": "Background: Early diagnosis of sepsis in children was essential to reducing mortality. This study aimed to explore the value of ferroptosis-related genes in children with sepsis.\nMethods: We screened the septic children microarray dataset from the GEO database and analyzed the ferroptosis-related differentially expressed genes (DEGs). A functional analysis of ferroptosis-related DEGs was performed. The protein-protein interaction network was used to identify hub genes. We explored the immune landscape of sepsis and controls. The value of hub genes in diagnosing sepsis was tested in the training (GSE26440) and validation sets (GSE13904), and ELISA was used to verify their diagnostic value in children with sepsis in our hospital.\nResults: A total of 2,103 DEGs in GSE26440 were obtained, of which ferroptosis-related DEGs were 34. Enrichment analysis showed significant enrichment in the ferroptosis and hypoxia pathways (i.e., HIF-1 pathway). The top three genes (HMOX1, MAPK14, TLR4) were selected as hub genes. Immunological analysis suggested that 10 cell types (i.e., CD8/CD4 T cells) were lower in sepsis. Immune checkpoint-related genes CD274 (PD-L1), HAVCR2 (TIM3), and SIGLEC15 were overexpressed in sepsis. The AUROC for the diagnosis of sepsis for HMOX1 and TLR4 ranged from 0.77 to 0.81, while the AUROC of MAPK14 reached 0.935 and 0.941 in the training and validation sets. Serum ELISA results of HMOX1 and TLR4 showed no significant difference in differentiating sepsis. The AUROC of MAPK14 was 0.877. When the diagnostic threshold was 74.852 ng/ml, the sensitivity and specificity were 0.906 and 0.719, respectively.\nConclusion: Ferroptosis-related gene MAPK14 is of considerable value in the early diagnosis of sepsis in children.", "claims": [{"id": "claim-method", "statement": "The diagnostic accuracy of three hub genes was analyzed with receiver operating characteristic curves (ROC) and expressed as the area under the ROC curves (AUROC) and 95% CI.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35844488", "locator": "sections[8] \"Statistical Analysis\" paragraph 2", "quote": "The diagnostic accuracy of three hub genes was analyzed with receiver operating characteristic curves (ROC) and expressed as the area under the ROC curves (AUROC) and 95% CI."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. 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The names of the repository/repositories and accession number(s) can be found in the article/supplementary material."}], "state": "complete"}, {"id": "claim-target-result", "statement": "MAPK14 was the ferroptosis-related hub gene with substantial diagnostic value for early diagnosis of sepsis in children.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35844488", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Ferroptosis-related gene MAPK14 is of considerable value in the early diagnosis of sepsis in children."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "MAPK14 was the ferroptosis-related hub gene with substantial diagnostic value for early diagnosis of sepsis in children.", "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:35844488"], "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:GSE13904"], "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:GSE13904"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35844488", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fimmu.2022.881914", "sha256": "sha256:7449d1466d2ed00e718f4b6b17d29e0eff0d95a060da4e7ba89be3dbe34a69ba", "bytes": 36337, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fimmu.2022.881914", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9281550", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE13904", "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=GSE13904", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE13904", "version": null, "note": "The datasets presented in this study can be found in online repositories. 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