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综合分析确定了甲状腺眼病和糖尿病中共同的治疗途径。

Integrative analysis identifies shared therapeutic pathways in thyroid eye disease and diabetes mellitus.

作者信息

Wang Yifei, Li Hui

机构信息

Beijing First Hospital of Integrated Chinese and Western Medicine,, No. 2, inside No. 13 Jintai Road, Chaoyang District, Beijing, China.

Beijing First Hospital of Integrated Chinese and Western Medicine, No. 2, inside No. 13 Jintai Road, Chaoyang District, Beijing, China.

出版信息

Sci Rep. 2025 Jul 10;15(1):24877. doi: 10.1038/s41598-025-08558-2.

DOI:10.1038/s41598-025-08558-2
PMID:40640313
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12246180/
Abstract

Thyroid eye disease (TED) and diabetes mellitus (DM) cause vision loss, with DM aggravating TED. In this study, we aimed to explore the mechanisms of this interaction, and therefore, analyzed gene expression data from representative TED and DM datasets using bioinformatic tools. Following normalization and differential expression analysis, common differentially expressed genes (CDEGs) between the datasets were identified and subjected to Gene Set Enrichment Analysis (GSEA), as well as Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses. Interaction networks were constructed and the diagnostic potential of the CDEGs was assessed using receiver operating characteristic (ROC) curve analysis. The TED_Dataset and DM_Dataset contained 449 and 108 DEGs, respectively, with seven CDEGs. GO and KEGG analyses linked the CDEGs to biological processes including leukocyte adhesion and apoptosis. GSEA emphasized their roles in inflammation and fibrosis. Protein-protein interaction network analysis identified MFAP4 as a key hub gene. Constructed mRNA-transcription factor, mRNA-RNA binding protein, mRNA-microRNA, and mRNA-drug interaction networks revealed extensive regulatory relationships. ROC curve analysis demonstrated that CXCL12 and SFRP4 were potential diagnostic biomarkers for TED, and SFRP4, IL6, MFAP4, and CRISPLD2 were potential diagnostic biomarkers for DM. Altogether, our findings provide comprehensive molecular insights into DM and TED, identifying novel targets for therapeutic intervention and diagnostic biomarkers.

摘要

甲状腺眼病(TED)和糖尿病(DM)会导致视力丧失,且糖尿病会加重甲状腺眼病。在本研究中,我们旨在探究这种相互作用的机制,因此,使用生物信息学工具分析了来自代表性甲状腺眼病和糖尿病数据集的基因表达数据。经过标准化和差异表达分析后,确定了数据集中的共同差异表达基因(CDEGs),并对其进行基因集富集分析(GSEA)以及基因本体(GO)和京都基因与基因组百科全书(KEGG)功能富集分析。构建了相互作用网络,并使用受试者工作特征(ROC)曲线分析评估了共同差异表达基因的诊断潜力。甲状腺眼病数据集和糖尿病数据集分别包含449个和108个差异表达基因,共有7个共同差异表达基因。GO和KEGG分析将这些共同差异表达基因与包括白细胞粘附和凋亡在内的生物学过程联系起来。GSEA强调了它们在炎症和纤维化中的作用。蛋白质-蛋白质相互作用网络分析确定MFAP4为关键枢纽基因。构建的mRNA-转录因子、mRNA-RNA结合蛋白、mRNA-微小RNA和mRNA-药物相互作用网络揭示了广泛的调控关系。ROC曲线分析表明,CXCL12和SFRP4是甲状腺眼病的潜在诊断生物标志物,而SFRP4、IL6、MFAP4和CRISPLD2是糖尿病的潜在诊断生物标志物。总之,我们的研究结果为糖尿病和甲状腺眼病提供了全面的分子见解,确定了治疗干预的新靶点和诊断生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4915/12246180/6b22491da3fd/41598_2025_8558_Fig8_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4915/12246180/6b22491da3fd/41598_2025_8558_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4915/12246180/ab23f43efc5a/41598_2025_8558_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4915/12246180/4ef224709c84/41598_2025_8558_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4915/12246180/68ac2c244717/41598_2025_8558_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4915/12246180/c60768daf06c/41598_2025_8558_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4915/12246180/6b22491da3fd/41598_2025_8558_Fig8_HTML.jpg

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本文引用的文献

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Unmet needs in the treatment of type 1 diabetes: why is it so difficult to achieve an improvement in metabolic control?1 型糖尿病治疗中的未满足需求:为什么改善代谢控制如此困难?
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CXCL16-dependent scavenging of oxidized lipids by islet macrophages promotes differentiation of pathogenic CD8 T cells in diabetic autoimmunity.
胰岛巨噬细胞通过 CXCL16 依赖性清除氧化脂质促进糖尿病自身免疫中致病性 CD8 T 细胞的分化。
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Type 2 diabetes.2型糖尿病
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TSH-SPP1/TRβ-TSH positive feedback loop mediates fat deposition of hepatocyte: Crosstalk between thyroid and liver.促甲状腺激素-分泌刺激磷蛋白 1/甲状腺受体β-促甲状腺激素正向反馈环介导肝细胞脂肪沉积:甲状腺与肝脏之间的串扰。
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