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pmid:39331243

Identification of key ferroptosis genes and subtypes in kidney renal clear cell carcinoma.

Biao Wang · Zhuo Wei · Man Xu · Hui Shu · Zheqi Fan

Discover oncology · 2024 doi:10.1007/s12672-024-01363-9

Paper

complete

Experiment

partial

Data

partial

Analysis

partial

Execution

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title
Identification of key ferroptosis genes and subtypes in kidney renal clear cell carcinoma.
doi
10.1007/s12672-024-01363-9
pmid
39331243
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Biao Wang
[1]
Zhuo Wei
[2]
Man Xu
[3]
Hui Shu
[4]
Zheqi Fan
journal
Discover oncology
year
2024
abstract
Tumour immunity is highly important for the occurrence and development of tumours, and many cancers are resistant to ferroptosis. This study aims to explore the relationship between ferroptosis-related genes (FRGs) and the immunological characteristics of kidney renal clear cell carcinoma (KIRC). We obtained RNA-seq profiles and clinical data of KIRC patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and identified CD44 and GLRX5 as the key FRGs involved in KIRC immune infiltration through Spearman's correlation analysis. Based on the expression of CD44 and GLRX5, the consensus clustering algorithm was used to classify the TCGA-KIRC samples into two clusters. A nomogram was constructed to evaluate the prognosis of KIRC patients. ESTIMATE, CIBERSORT, and single-sample gene set enrichment analysis (ssGSEA) were performed to evaluate immune infiltration between the two clusters. A weighted gene co-expression network analysis (WGCNA) was used to identify the most relevant genes to the clusters and immunity. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. The external dataset GSE53757 was used to validate the immunological features between the two clusters. Cluster 2 patients had more active immune infiltration and might be more sensitive to immunotherapy; Cluster 2 patients also had a worse prognosis and might be at a more advanced stage of KIRC. We identified key ferroptosis-related genes and subgroups involved in the immune infiltration of KIRC, which is highly important for exploring the molecular mechanisms and treatments of KIRC.
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We obtained RNA-seq profiles and clinical data of KIRC patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and identified CD44 and GLRX5 as the key FRGs involved in KIRC immune infiltration through Spearman’s correlation analysis.
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We obtained RNA-seq profiles and clinical data of KIRC patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and identified CD44 and GLRX5 as the key FRGs involved in KIRC immune infiltration through Spearman’s correlation analysis.
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Publicly available datasets were analyzed in this study. These data can be found in TCGA (http://cancergenome.nih.gov/), GEO (https://www.ncbi.nlm.nih.gov/geo/), HPA (https://www.proteinatlas.org/), and FerrDb (http://www.zhounan.org/ferrdb/current/).
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Publicly available datasets were analyzed in this study. These data can be found in TCGA (http://cancergenome.nih.gov/), GEO (https://www.ncbi.nlm.nih.gov/geo/), HPA (https://www.proteinatlas.org/), and FerrDb (http://www.zhounan.org/ferrdb/current/).
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CD44 and GLRX5 were identified as key ferroptosis-related genes involved in KIRC immune infiltration, with clustering and immune-infiltration analyses conducted using TCGA-KIRC data and validated in GSE53757.
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We obtained RNA-seq profiles and clinical data of KIRC patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and identified CD44 and GLRX5 as the key FRGs involved in KIRC immune infiltration through Spearman’s correlation analysis.
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Considering that they had the strongest correlation with immune scores, CD44 and GLRX5 were included in the subsequent analysis.
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The results indicated that tumour immune infiltration was more active in Cluster 2 than in Cluster 1 in the GEO cohort, which was consistent with the results in the TCGA cohort.
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Gene array analysis of clear cell renal cell carcinoma tissue versus matched normal kidney tissue
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We obtained RNA-seq profiles and clinical data of KIRC patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and identified CD44 and GLRX5 as the key FRGs involved in KIRC immune infiltration through Spearman’s correlation analysis.
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nal clear cell carcinoma (KIRC). We obtained RNA-seq profiles and clinical data of KIRC patients
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l cancer through the HPA database (Fig. 2A). Immunohistochemistry revealed increased protein expression of CD4
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39331243", "kind": "science-record", "revision": 3, "content_hash": "sha256:edaa040980e0070f08d5b8b14167ddeb234a334ec6a5732fa164f4e1c86c09f6", "created_at": "2026-11-01T20:29:31Z", "updated_at": "2026-11-01T22:12:46Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of key ferroptosis genes and subtypes in kidney renal clear cell carcinoma.", "doi": "10.1007/s12672-024-01363-9", "pmid": "39331243", "authors": ["Biao Wang", "Zhuo Wei", "Man Xu", "Hui Shu", "Zheqi Fan"], "journal": "Discover oncology", "year": 2024, "abstract": "Tumour immunity is highly important for the occurrence and development of tumours, and many cancers are resistant to ferroptosis. This study aims to explore the relationship between ferroptosis-related genes (FRGs) and the immunological characteristics of kidney renal clear cell carcinoma (KIRC). We obtained RNA-seq profiles and clinical data of KIRC patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and identified CD44 and GLRX5 as the key FRGs involved in KIRC immune infiltration through Spearman's correlation analysis. Based on the expression of CD44 and GLRX5, the consensus clustering algorithm was used to classify the TCGA-KIRC samples into two clusters. A nomogram was constructed to evaluate the prognosis of KIRC patients. ESTIMATE, CIBERSORT, and single-sample gene set enrichment analysis (ssGSEA) were performed to evaluate immune infiltration between the two clusters. A weighted gene co-expression network analysis (WGCNA) was used to identify the most relevant genes to the clusters and immunity. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. The external dataset GSE53757 was used to validate the immunological features between the two clusters. Cluster 2 patients had more active immune infiltration and might be more sensitive to immunotherapy; Cluster 2 patients also had a worse prognosis and might be at a more advanced stage of KIRC. We identified key ferroptosis-related genes and subgroups involved in the immune infiltration of KIRC, which is highly important for exploring the molecular mechanisms and treatments of KIRC.", "claims": [{"id": "claim-method", "statement": "We obtained RNA-seq profiles and clinical data of KIRC patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and identified CD44 and GLRX5 as the key FRGs involved in KIRC immune infiltration through Spearman’s correlation analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39331243", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "We obtained RNA-seq profiles and clinical data of KIRC patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and identified CD44 and GLRX5 as the key FRGs involved in KIRC immune infiltration through Spearman’s correlation analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. These data can be found in TCGA (http://cancergenome.nih.gov/), GEO (https://www.ncbi.nlm.nih.gov/geo/), HPA (https://www.proteinatlas.org/), and FerrDb (http://www.zhounan.org/ferrdb/current/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39331243", "locator": "sections[30] \"Data availability\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. These data can be found in TCGA (http://cancergenome.nih.gov/), GEO (https://www.ncbi.nlm.nih.gov/geo/), HPA (https://www.proteinatlas.org/), and FerrDb (http://www.zhounan.org/ferrdb/current/)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "CD44 and GLRX5 were identified as key ferroptosis-related genes involved in KIRC immune infiltration, with clustering and immune-infiltration analyses conducted using TCGA-KIRC data and validated in GSE53757.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39331243", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "We obtained RNA-seq profiles and clinical data of KIRC patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and identified CD44 and GLRX5 as the key FRGs involved in KIRC immune infiltration through Spearman’s correlation analysis."}, {"asset": "source:pmid:39331243", "locator": "sections[16] \"Identification of differentially expressed overlapping immune-related genes\" paragraph 4", "quote": "Considering that they had the strongest correlation with immune scores, CD44 and GLRX5 were included in the subsequent analysis."}, {"asset": "source:pmid:39331243", "locator": "sections[22] \"Verification of clustering and the effects of CD44 and GLRX5\" paragraph 2", "quote": "The results indicated that tumour immune infiltration was more active in Cluster 2 than in Cluster 1 in the GEO cohort, which was consistent with the results in the TCGA cohort."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "CD44 and GLRX5 were identified as key ferroptosis-related genes involved in KIRC immune infiltration, with clustering and immune-infiltration analyses conducted using TCGA-KIRC data and validated in GSE53757.", "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:39331243"], "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:GSE53757"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:group_comparison_wilcoxon", "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:GSE53757"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_wilcoxon"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:39331243", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1007/s12672-024-01363-9", "sha256": "sha256:471704e4a702b9c276efb96e1b25c090d58241c34e690de57cb109a9ab1341d5", "bytes": 55743, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1007/s12672-024-01363-9", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11436560", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE53757", "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=GSE53757", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE53757", "version": null, "note": "Publicly available datasets were analyzed in this study. These data can be found in TCGA (http://cancergenome.nih.gov/), GEO (https://www.ncbi.nlm.nih.gov/geo/), HPA (https://www.proteinatlas.org/), and FerrDb (http://www.zhounan.org/ferrdb/current/).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. These data can be found in TCGA (http://cancergenome.nih.gov/), GEO (https://www.ncbi.nlm.nih.gov/geo/), HPA (https://www.proteinatlas.org/), and FerrDb (http://www.zhounan.org/ferrdb/current/).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1300062", "GSM1300063", "GSM1300064", "GSM1300065", "GSM1300066", "GSM1300067", "GSM1300068", "GSM1300069", "GSM1300070", "GSM1300071", "GSM1300072", "GSM1300073", "GSM1300074", "GSM1300075", "GSM1300076", "GSM1300077", "GSM1300078", "GSM1300079", "GSM1300080", "GSM1300081", "GSM1300082", "GSM1300083", "GSM1300084", "GSM1300085", "GSM1300086", "GSM1300087", "GSM1300088", "GSM1300089", "GSM1300090", "GSM1300091", "GSM1300092", "GSM1300093", "GSM1300094", "GSM1300095", "GSM1300096", "GSM1300097", "GSM1300098", "GSM1300099", "GSM1300100", "GSM1300101", "GSM1300102", "GSM1300103", "GSM1300104", "GSM1300105", "GSM1300106", "GSM1300107", "GSM1300108", "GSM1300109", "GSM1300110", "GSM1300111", "GSM1300112", 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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": ["GSE53757"], "resolved_accessions": ["GSE53757"], "statements": ["Publicly available datasets were analyzed in this study. These data can be found in TCGA (http://cancergenome.nih.gov/), GEO (https://www.ncbi.nlm.nih.gov/geo/), HPA (https://www.proteinatlas.org/), and FerrDb (http://www.zhounan.org/ferrdb/current/)."], "basis": "The paper names GSE53757 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. 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