Exploring the comorbidity mechanisms between atherosclerosis and hashimoto’s thyroiditis based on microarray and single-cell sequencing analysis
Abstract Atherosclerosis (AS) is a chronic vascular disease characterized by inflammation of the arterial wall and the formation of cholesterol plaques. Hashimoto’s thyroiditis (HT) is an autoimmune disorder marked by chronic inflammation and destruction of thyroid tissue. Although previous studies...
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Nature Portfolio
2025-01-01
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| author | Yirong Ma Shuguang Wu Junyu Lai Qiang Wan Jingxuan Hu Yanhong Liu Ziyi Zhou Jianguang Wu |
| author_facet | Yirong Ma Shuguang Wu Junyu Lai Qiang Wan Jingxuan Hu Yanhong Liu Ziyi Zhou Jianguang Wu |
| author_sort | Yirong Ma |
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| description | Abstract Atherosclerosis (AS) is a chronic vascular disease characterized by inflammation of the arterial wall and the formation of cholesterol plaques. Hashimoto’s thyroiditis (HT) is an autoimmune disorder marked by chronic inflammation and destruction of thyroid tissue. Although previous studies have identified common risk factors between AS and HT, the specific etiology and pathogenic mechanisms underlying these associations remain unclear. We obtained relevant datasets for AS and HT from the Gene Expression Omnibus (GEO). By employing the Limma package, we pinpointed common differentially expressed genes (DEGs) and discerned co-expression modules linked to AS and HT via Weighted Gene Co-expression Network Analysis (WGCNA). We elucidated gene functions and regulatory networks across various biological scenarios through enrichment and pathway analysis using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Core genes were identified using Cytoscape software and further validated with external datasets. We also conducted immune infiltration analysis on these core genes utilizing the CIBERSORT method. Lastly, Single-cell analysis was instrumental in uncovering common diagnostic markers. Based on differential analysis and WGCNA, we identified 119 candidate genes within the cohorts for AS and HT. KEGG and GO enrichment analyses indicate that these genes are significantly involved in antigen processing and presentation, along with various immune-inflammatory pathways. Two pivotal genes, PTPRC and TYROBP, were identified using five algorithms from the cytoHubba plugin. Validation through external datasets confirmed their substantial diagnostic value for AS and HT. Moreover, the results of Gene Set Enrichment Analysis (GSEA) indicated that these core genes are significantly enriched in various receptor interactions and signaling pathways. Immune infiltration analysis revealed a strong association of lymphocytes and macrophages with the pathogenesis of AS and HT. Single-cell analysis demonstrated predominant expression of the core genes in macrophages, monocytes, T cells and Common Myeloid Progenitor (CMP). This study proposes that an aberrant immune response might represent a shared pathogenic mechanism in AS and HT. The genes PTPRC and TYROBP are identified as critical potential biomarkers and therapeutic targets for these comorbid conditions. Furthermore, the core genes and their interactions with immune cells could serve as promising targets for future diagnostic and therapeutic strategies. |
| format | Article |
| id | doaj-art-15c9806ac32747c38f2ea79e92203252 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-15c9806ac32747c38f2ea79e922032522025-01-19T12:20:30ZengNature PortfolioScientific Reports2045-23222025-01-0115111710.1038/s41598-025-85112-0Exploring the comorbidity mechanisms between atherosclerosis and hashimoto’s thyroiditis based on microarray and single-cell sequencing analysisYirong Ma0Shuguang Wu1Junyu Lai2Qiang Wan3Jingxuan Hu4Yanhong Liu5Ziyi Zhou6Jianguang Wu7Department of Postgraduate, Jiangxi University of Chinese MedicineNeurology Department, Jiangxi Province Hospital of Integrated Chinese & Western MedicineCardiology Department, Affiliated Hospital of Jiangxi University of Chinese MedicineCardiology Department, Affiliated Hospital of Jiangxi University of Chinese MedicineDepartment of Postgraduate, Jiangxi University of Chinese MedicineDepartment of Postgraduate, Jiangxi University of Chinese MedicineDepartment of Postgraduate, Jiangxi University of Chinese MedicineCardiology Department, Affiliated Hospital of Jiangxi University of Chinese MedicineAbstract Atherosclerosis (AS) is a chronic vascular disease characterized by inflammation of the arterial wall and the formation of cholesterol plaques. Hashimoto’s thyroiditis (HT) is an autoimmune disorder marked by chronic inflammation and destruction of thyroid tissue. Although previous studies have identified common risk factors between AS and HT, the specific etiology and pathogenic mechanisms underlying these associations remain unclear. We obtained relevant datasets for AS and HT from the Gene Expression Omnibus (GEO). By employing the Limma package, we pinpointed common differentially expressed genes (DEGs) and discerned co-expression modules linked to AS and HT via Weighted Gene Co-expression Network Analysis (WGCNA). We elucidated gene functions and regulatory networks across various biological scenarios through enrichment and pathway analysis using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Core genes were identified using Cytoscape software and further validated with external datasets. We also conducted immune infiltration analysis on these core genes utilizing the CIBERSORT method. Lastly, Single-cell analysis was instrumental in uncovering common diagnostic markers. Based on differential analysis and WGCNA, we identified 119 candidate genes within the cohorts for AS and HT. KEGG and GO enrichment analyses indicate that these genes are significantly involved in antigen processing and presentation, along with various immune-inflammatory pathways. Two pivotal genes, PTPRC and TYROBP, were identified using five algorithms from the cytoHubba plugin. Validation through external datasets confirmed their substantial diagnostic value for AS and HT. Moreover, the results of Gene Set Enrichment Analysis (GSEA) indicated that these core genes are significantly enriched in various receptor interactions and signaling pathways. Immune infiltration analysis revealed a strong association of lymphocytes and macrophages with the pathogenesis of AS and HT. Single-cell analysis demonstrated predominant expression of the core genes in macrophages, monocytes, T cells and Common Myeloid Progenitor (CMP). This study proposes that an aberrant immune response might represent a shared pathogenic mechanism in AS and HT. The genes PTPRC and TYROBP are identified as critical potential biomarkers and therapeutic targets for these comorbid conditions. Furthermore, the core genes and their interactions with immune cells could serve as promising targets for future diagnostic and therapeutic strategies.https://doi.org/10.1038/s41598-025-85112-0AtherosclerosisHashimoto’s thyroiditisBioinformaticsImmune infiltration analysisMicroarray analysisSingle-cell sequencing analysis |
| spellingShingle | Yirong Ma Shuguang Wu Junyu Lai Qiang Wan Jingxuan Hu Yanhong Liu Ziyi Zhou Jianguang Wu Exploring the comorbidity mechanisms between atherosclerosis and hashimoto’s thyroiditis based on microarray and single-cell sequencing analysis Scientific Reports Atherosclerosis Hashimoto’s thyroiditis Bioinformatics Immune infiltration analysis Microarray analysis Single-cell sequencing analysis |
| title | Exploring the comorbidity mechanisms between atherosclerosis and hashimoto’s thyroiditis based on microarray and single-cell sequencing analysis |
| title_full | Exploring the comorbidity mechanisms between atherosclerosis and hashimoto’s thyroiditis based on microarray and single-cell sequencing analysis |
| title_fullStr | Exploring the comorbidity mechanisms between atherosclerosis and hashimoto’s thyroiditis based on microarray and single-cell sequencing analysis |
| title_full_unstemmed | Exploring the comorbidity mechanisms between atherosclerosis and hashimoto’s thyroiditis based on microarray and single-cell sequencing analysis |
| title_short | Exploring the comorbidity mechanisms between atherosclerosis and hashimoto’s thyroiditis based on microarray and single-cell sequencing analysis |
| title_sort | exploring the comorbidity mechanisms between atherosclerosis and hashimoto s thyroiditis based on microarray and single cell sequencing analysis |
| topic | Atherosclerosis Hashimoto’s thyroiditis Bioinformatics Immune infiltration analysis Microarray analysis Single-cell sequencing analysis |
| url | https://doi.org/10.1038/s41598-025-85112-0 |
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