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pmid:34386492

Analysis of Ferroptosis-Mediated Modification Patterns and Tumor Immune Microenvironment Characterization in Uveal Melanoma.

Yi Jin · Zhanwang Wang · Dong He · Yuxing Zhu · Lian Gong · Mengqing Xiao · Xingyu Chen · Ke Cao

Frontiers in cell and developmental biology · 2021 doi:10.3389/fcell.2021.685120

Paper

complete

Experiment

partial

Data

partial

Analysis

partial

Execution

absent

Execution evidence has not yet been added to this .science file. Explore its methods, data and open questions to plan the next step.
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title
Analysis of Ferroptosis-Mediated Modification Patterns and Tumor Immune Microenvironment Characterization in Uveal Melanoma.
doi
10.3389/fcell.2021.685120
pmid
34386492
authors array · 8 items
[0]
Yi Jin
[1]
Zhanwang Wang
[2]
Dong He
[3]
Yuxing Zhu
[4]
Lian Gong
[5]
Mengqing Xiao
[6]
Xingyu Chen
[7]
Ke Cao
journal
Frontiers in cell and developmental biology
year
2021
abstract
Uveal melanoma (UVM) is an intraocular malignancy in adults in which approximately 50% of patients develop metastatic disease and have a poor prognosis. The need for immunotherapies has rapidly emerged, and recent research has yielded impressive results. Emerging evidence has implicated ferroptosis as a novel type of cell death that may mediate tumor-infiltrating immune cells to influence anticancer immunity. In this study, we first selected 11 ferroptosis regulators in UVM samples from the training set (TCGA and GSE84976 databases) by Cox analysis. We then divided these molecules into modules A and B based on the STRING database and used consensus clustering analysis to classify genes in both modules. According to the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA), the results revealed that the clusters in module A were remarkably related to immune-related pathways. Next, we applied the ESTIMATE and CIBERSORT algorithms and found that these ferroptosis-related patterns may affect a proportion of TME infiltrating cells, thereby mediating the tumor immune environment. Additionally, to further develop the prognostic signatures based on the immune landscape, we established a six-gene-regulator prognostic model in the training set and successfully verified it in the validation set (GSE44295 and GSE27831). Subsequently, we identified the key molecules, including ABCC1, CHAC1, and GSS, which were associated with poor overall survival, progression-free survival, disease-specific survival, and progression-free interval. We constructed a competing endogenous RNA network to further elucidate the mechanisms, which consisted of 29 lncRNAs, 12 miRNAs, and 25 ferroptosis-related mRNAs. Our findings indicate that the ferroptosis-related genes may be suitable potential biomarkers to provide novel insights into UVM prognosis and decipher the underlying mechanisms in tumor microenvironment characterization.
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Syntenin-1 is expressed in uveal melanoma and correlates with metastatic progression
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Upregulation of HLA expression in primary Uveal Melanoma by infiltrating leukocytes
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34386492", "kind": "science-record", "revision": 7, "content_hash": "sha256:305f22e6b0ec04ce58c9a6c15c5485d88caa884801fcdcb0bfc45e18d2bf8464", "created_at": "2026-11-01T15:41:47Z", "updated_at": "2026-11-01T22:04:28Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Analysis of Ferroptosis-Mediated Modification Patterns and Tumor Immune Microenvironment Characterization in Uveal Melanoma.", "doi": "10.3389/fcell.2021.685120", "pmid": "34386492", "authors": ["Yi Jin", "Zhanwang Wang", "Dong He", "Yuxing Zhu", "Lian Gong", "Mengqing Xiao", "Xingyu Chen", "Ke Cao"], "journal": "Frontiers in cell and developmental biology", "year": 2021, "abstract": "Uveal melanoma (UVM) is an intraocular malignancy in adults in which approximately 50% of patients develop metastatic disease and have a poor prognosis. The need for immunotherapies has rapidly emerged, and recent research has yielded impressive results. Emerging evidence has implicated ferroptosis as a novel type of cell death that may mediate tumor-infiltrating immune cells to influence anticancer immunity. In this study, we first selected 11 ferroptosis regulators in UVM samples from the training set (TCGA and GSE84976 databases) by Cox analysis. We then divided these molecules into modules A and B based on the STRING database and used consensus clustering analysis to classify genes in both modules. According to the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA), the results revealed that the clusters in module A were remarkably related to immune-related pathways. Next, we applied the ESTIMATE and CIBERSORT algorithms and found that these ferroptosis-related patterns may affect a proportion of TME infiltrating cells, thereby mediating the tumor immune environment. Additionally, to further develop the prognostic signatures based on the immune landscape, we established a six-gene-regulator prognostic model in the training set and successfully verified it in the validation set (GSE44295 and GSE27831). Subsequently, we identified the key molecules, including ABCC1, CHAC1, and GSS, which were associated with poor overall survival, progression-free survival, disease-specific survival, and progression-free interval. We constructed a competing endogenous RNA network to further elucidate the mechanisms, which consisted of 29 lncRNAs, 12 miRNAs, and 25 ferroptosis-related mRNAs. Our findings indicate that the ferroptosis-related genes may be suitable potential biomarkers to provide novel insights into UVM prognosis and decipher the underlying mechanisms in tumor microenvironment characterization.", "claims": [{"id": "claim-method", "statement": "Cox proportional hazard regression analyses were used to select the independent prognostic value of OS, including clinical characteristics and ferroptosis regulators.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34386492", "locator": "sections[10] \"Statistical Analysis\" paragraph 2", "quote": "Cox proportional hazard regression analyses were used to select the independent prognostic value of OS, including clinical characteristics and ferroptosis regulators."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. 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This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE27831"], "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:GSE27831"], "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:34386492", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fcell.2021.685120", "sha256": "sha256:d772c412cd619c9ad58f62186a36968e8b91682c4af534b7e09241646175e342", "bytes": 60402, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fcell.2021.685120", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8353259", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE27831", "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=GSE27831", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE27831", "version": null, "note": "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.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "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.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM685470", "GSM685471", "GSM685472", "GSM685473", "GSM685474", "GSM685475", "GSM685522", "GSM685523", "GSM685601", "GSM685602", "GSM685603", "GSM685650", "GSM685651", "GSM685652", "GSM686961", "GSM686962", "GSM686963", "GSM686984", "GSM686985", "GSM686986", "GSM686987", "GSM686988", "GSM686989", "GSM686990", "GSM686991", "GSM687001", "GSM687002", "GSM687003", "GSM687004"], "sample_count": 29, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Syntenin-1 is expressed in uveal melanoma and correlates with metastatic progression ", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE44295", "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=GSE44295", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE44295", "version": null, "note": "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.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets presented in this study can be found in online repositories. 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