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pmid:37021001

Identification and validation of ferroptosis-related genes and immune cell infiltration in thyroid associated ophthalmopathy.

Sainan Chen · Jiale Diao · Zifan Yue · Ruili Wei

Frontiers in genetics · 2023 doi:10.3389/fgene.2023.1118391

Paper

complete

Experiment

complete

Data

partial

Analysis

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Execution

absent

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title
Identification and validation of ferroptosis-related genes and immune cell infiltration in thyroid associated ophthalmopathy.
doi
10.3389/fgene.2023.1118391
pmid
37021001
authors array · 4 items
[0]
Sainan Chen
[1]
Jiale Diao
[2]
Zifan Yue
[3]
Ruili Wei
journal
Frontiers in genetics
year
2023
abstract
Thyroid associated ophthalmopathy (TAO) is an orbital autoimmune inflammatory disease that is commonly associated with thyroid dysfunction. Although the etiology of TAO is unclear, ROS accumulation and oxidative stress have been closely linked to the pathogenesis of TAO. Ferroptosis is an iron-dependent programmed cell death characterized by intracellular labile iron levels, excessive accumulation of reactive oxygen species (ROS) and lipid peroxidation. Currently, there are few reports regarding the role of ferroptosis in TAO. This article aimed to identify ferroptosis-related genes (FRGs) with diagnostic and therapeutic potential in TAO and explore their relationship with immune cells and lncRNAs. GSE58331 was downloaded from Gene Expression Omnibus (GEO) database. A total of 162 DEGs were identified between 27 TAO samples and 22 health samples from GSE58331, among which six FRGs (CYBB, CTSB, SLC38A1, TLR4, PEX3, and ABCC1) were obtained. The AUC of SLC38A1, TLR4, PEX3 in lacrimal gland tissues was greater than 80 which suggested high diagnostic value in TAO. The result of immune cell infiltrate analysis indicated increased infiltration of monocytes (p < 0.001), macrophages M0(p = 0.039), mast cells activated (p = 0.008), and neutrophils (p = 0.045) in orbital tissues from TAO patients. Meanwhile, mast cells resting (p = 0.043) and macrophages M2 (p = 0.02) showed reduced infiltration in TAO samples. There were no gender differences in immune cell infiltration in the TAO patients. Two differentially expressed lncRNAs, LINC01140 and ZFHX4-AS1, in TAO groups were identified as ferroptosis-related lncRNAs. CYBB-LINC01140-TLR4, CYBB- LINC01140- SLC38A1, TLR4- LINC01140- SLC38A1, and CTSB- ZFHX4-AS1- CYBB may be potential RNA regulatory pathways in TAO. Targeted drugs and transcription factors for differential expressed FRGs were also screened out in our study. In vitro, experiments revealed that CTSB, PEX3, ABCC1 and ZFHX4-AS1(lncRNA) were differentially expressed in orbital fibroblasts (OFs) between TAO groups and healthy controls at the transcriptional level.
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The Limma R package was used to identify differential expressed lncRNAs in TAO groups. The Pearson correlation analysis was utilized to investigate the co-expression of differential expressed lncRNAs and FRGs in the gene matrix.
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The Limma R package was used to identify differential expressed lncRNAs in TAO groups. The Pearson correlation analysis was utilized to investigate the co-expression of differential expressed lncRNAs and FRGs in the gene matrix.
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Two differentially expressed lncRNAs, LINC01140 and ZFHX4-AS1, in TAO groups were identified as ferroptosis-related lncRNAs.
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Two differentially expressed lncRNAs, LINC01140 and ZFHX4-AS1, in TAO groups were identified as ferroptosis-related lncRNAs.
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{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37021001", "kind": "science-record", "revision": 4, "content_hash": "sha256:01d212ffc2bf456f4b7dc88751c4ed6fc5549e0ba700df3c4ccf3189e202a5ea", "created_at": "2026-11-01T19:01:40Z", "updated_at": "2026-11-01T22:51:38Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and validation of ferroptosis-related genes and immune cell infiltration in thyroid associated ophthalmopathy.", "doi": "10.3389/fgene.2023.1118391", "pmid": "37021001", "authors": ["Sainan Chen", "Jiale Diao", "Zifan Yue", "Ruili Wei"], "journal": "Frontiers in genetics", "year": 2023, "abstract": "Thyroid associated ophthalmopathy (TAO) is an orbital autoimmune inflammatory disease that is commonly associated with thyroid dysfunction. Although the etiology of TAO is unclear, ROS accumulation and oxidative stress have been closely linked to the pathogenesis of TAO. Ferroptosis is an iron-dependent programmed cell death characterized by intracellular labile iron levels, excessive accumulation of reactive oxygen species (ROS) and lipid peroxidation. Currently, there are few reports regarding the role of ferroptosis in TAO. This article aimed to identify ferroptosis-related genes (FRGs) with diagnostic and therapeutic potential in TAO and explore their relationship with immune cells and lncRNAs. GSE58331 was downloaded from Gene Expression Omnibus (GEO) database. A total of 162 DEGs were identified between 27 TAO samples and 22 health samples from GSE58331, among which six FRGs (CYBB, CTSB, SLC38A1, TLR4, PEX3, and ABCC1) were obtained. The AUC of SLC38A1, TLR4, PEX3 in lacrimal gland tissues was greater than 80 which suggested high diagnostic value in TAO. The result of immune cell infiltrate analysis indicated increased infiltration of monocytes (p < 0.001), macrophages M0(p = 0.039), mast cells activated (p = 0.008), and neutrophils (p = 0.045) in orbital tissues from TAO patients. Meanwhile, mast cells resting (p = 0.043) and macrophages M2 (p = 0.02) showed reduced infiltration in TAO samples. There were no gender differences in immune cell infiltration in the TAO patients. Two differentially expressed lncRNAs, LINC01140 and ZFHX4-AS1, in TAO groups were identified as ferroptosis-related lncRNAs. CYBB-LINC01140-TLR4, CYBB- LINC01140- SLC38A1, TLR4- LINC01140- SLC38A1, and CTSB- ZFHX4-AS1- CYBB may be potential RNA regulatory pathways in TAO. Targeted drugs and transcription factors for differential expressed FRGs were also screened out in our study. In vitro, experiments revealed that CTSB, PEX3, ABCC1 and ZFHX4-AS1(lncRNA) were differentially expressed in orbital fibroblasts (OFs) between TAO groups and healthy controls at the transcriptional level.", "claims": [{"id": "claim-method", "statement": "The Limma R package was used to identify differential expressed lncRNAs in TAO groups. The Pearson correlation analysis was utilized to investigate the co-expression of differential expressed lncRNAs and FRGs in the gene matrix.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37021001", "locator": "sections[7] \"Identification of the ferroptosis-related lncRNAs\" paragraph 2", "quote": "The Limma R package was used to identify differential expressed lncRNAs in TAO groups. The Pearson correlation analysis was utilized to investigate the co-expression of differential expressed lncRNAs and FRGs in the gene matrix."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37021001", "locator": "sections[22] \"Data availability statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Two differentially expressed lncRNAs, LINC01140 and ZFHX4-AS1, in TAO groups were identified as ferroptosis-related lncRNAs.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37021001", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Two differentially expressed lncRNAs, LINC01140 and ZFHX4-AS1, in TAO groups were identified as ferroptosis-related lncRNAs."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Two differentially expressed lncRNAs, LINC01140 and ZFHX4-AS1, in TAO groups were identified as ferroptosis-related lncRNAs.", "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:37021001"], "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:GSE58331"], "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:GSE58331"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37021001", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fgene.2023.1118391", "sha256": "sha256:82b0ba463d7a864f5c3b8c4d90362d5e6794c22b9302b94dc83414de617ec954", "bytes": 37901, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fgene.2023.1118391", "version": null, "note": "Full article fetched from PMC; 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