Uncovering the Interplay of Ferroptosis and Immune System in Coronary Artery Disease: Construction and Validation of a Diagnostic Model
Zhiyong Zhang, Xiaoming Zhu, Tao Zhang, Chuang Li, Dapeng Zhang, Weiming Li, Lin Zhao Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of ChinaCorrespondence: Lin Zhao, Heart Center and Beijing Key Labo...
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Dove Medical Press
2025-07-01
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| author | Zhang Z Zhu X Zhang T Li C Zhang D Li W Zhao L |
| author_facet | Zhang Z Zhu X Zhang T Li C Zhang D Li W Zhao L |
| author_sort | Zhang Z |
| collection | DOAJ |
| description | Zhiyong Zhang, Xiaoming Zhu, Tao Zhang, Chuang Li, Dapeng Zhang, Weiming Li, Lin Zhao Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of ChinaCorrespondence: Lin Zhao, Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, No. 8 Gongti South Road, Chaoyang District, Beijing, 100020, People’s Republic of China, Email trichina2007@126.comObjective: To explore the roles of ferroptosis and immune regulation in coronary artery disease (CAD) and find potential diagnostic biomarkers.Methods: Three gene expression profile datasets were used, with GSE202625 as the training set and GSE42148 and GSE180081 as validation sets. LIMMA identified differentially expressed genes (DEGs) between CAD and control groups. ClusterProfiler conducted functional enrichment analysis. Ferroptosis-related genes from FerrDb were intersected with DEGs. ssGSEA and Pearson analysis analyzed immune cell subsets. LASSO built a diagnostic model. In vitro and in vivo experiments included qPCR, ELISA, pathological examination, and Western blot.Results: In the GSE202625 dataset, 70 genes were upregulated and 895 genes were downregulated in CAD samples. A total of 29 ferroptosis-associated DEGs were identified, and immune cell profiling revealed differences in immune cell subsets between CAD and healthy cohorts. LASSO identified six genes (IDH1, MMD, NDRG1, WIPI1, BID, and TRIM26) for the diagnostic model, which collectively achieved an AUC of 0.904 in the training dataset, 0.776 in the GSE180081 validation dataset, and 0.902 in the GSE42148 validation dataset. IDH1 had the highest diagnostic efficacy with an AUC of 0.821. Clinically, 26 CAD patients (angiographically confirmed, ≥ 50% luminal stenosis) and 12 controls showed that CAD patients had higher prevalence of hypertension, diabetes, and elevated lipid markers. IDH1 was downregulated in CAD patients and inversely correlated with the Gensini score. In the CAD mouse model, IDH1 expression was decreased in aortic tissues.Conclusion: Six genes correlated with CAD, and the multi-gene diagnostic model performed well. IDH1 was a potential CAD biomarker, aiding CAD diagnosis and treatment research. Keywords: coronary artery disease, ferroptosis, immune regulation, biomarkers, disease diagnosis |
| format | Article |
| id | doaj-art-ed5404822cfe4ae08ededd3343acc0db |
| institution | Kabale University |
| issn | 1178-7074 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Dove Medical Press |
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| series | International Journal of General Medicine |
| spelling | doaj-art-ed5404822cfe4ae08ededd3343acc0db2025-08-20T03:50:44ZengDove Medical PressInternational Journal of General Medicine1178-70742025-07-01Volume 18Issue 139013917104818Uncovering the Interplay of Ferroptosis and Immune System in Coronary Artery Disease: Construction and Validation of a Diagnostic ModelZhang Z0Zhu X1Zhang T2Li C3Zhang D4Li W5Zhao L6Heart Center and Beijing Key Laboratory of HypertensionHeart Center and Beijing Key Laboratory of HypertensionHeart Center and Beijing Key Laboratory of HypertensionHeart Center and Beijing Key Laboratory of HypertensionHeart Center and Beijing Key Laboratory of HypertensionHeart Center and Beijing Key Laboratory of HypertensionHeart Center and Beijing Key Laboratory of HypertensionZhiyong Zhang, Xiaoming Zhu, Tao Zhang, Chuang Li, Dapeng Zhang, Weiming Li, Lin Zhao Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of ChinaCorrespondence: Lin Zhao, Heart Center and Beijing Key Laboratory of Hypertension, Beijing Chaoyang Hospital, Capital Medical University, No. 8 Gongti South Road, Chaoyang District, Beijing, 100020, People’s Republic of China, Email trichina2007@126.comObjective: To explore the roles of ferroptosis and immune regulation in coronary artery disease (CAD) and find potential diagnostic biomarkers.Methods: Three gene expression profile datasets were used, with GSE202625 as the training set and GSE42148 and GSE180081 as validation sets. LIMMA identified differentially expressed genes (DEGs) between CAD and control groups. ClusterProfiler conducted functional enrichment analysis. Ferroptosis-related genes from FerrDb were intersected with DEGs. ssGSEA and Pearson analysis analyzed immune cell subsets. LASSO built a diagnostic model. In vitro and in vivo experiments included qPCR, ELISA, pathological examination, and Western blot.Results: In the GSE202625 dataset, 70 genes were upregulated and 895 genes were downregulated in CAD samples. A total of 29 ferroptosis-associated DEGs were identified, and immune cell profiling revealed differences in immune cell subsets between CAD and healthy cohorts. LASSO identified six genes (IDH1, MMD, NDRG1, WIPI1, BID, and TRIM26) for the diagnostic model, which collectively achieved an AUC of 0.904 in the training dataset, 0.776 in the GSE180081 validation dataset, and 0.902 in the GSE42148 validation dataset. IDH1 had the highest diagnostic efficacy with an AUC of 0.821. Clinically, 26 CAD patients (angiographically confirmed, ≥ 50% luminal stenosis) and 12 controls showed that CAD patients had higher prevalence of hypertension, diabetes, and elevated lipid markers. IDH1 was downregulated in CAD patients and inversely correlated with the Gensini score. In the CAD mouse model, IDH1 expression was decreased in aortic tissues.Conclusion: Six genes correlated with CAD, and the multi-gene diagnostic model performed well. IDH1 was a potential CAD biomarker, aiding CAD diagnosis and treatment research. Keywords: coronary artery disease, ferroptosis, immune regulation, biomarkers, disease diagnosishttps://www.dovepress.com/uncovering-the-interplay-of-ferroptosis-and-immune-system-in-coronary--peer-reviewed-fulltext-article-IJGMCoronary artery diseaseFerroptosisImmune regulationBiomarkersDisease diagnosis |
| spellingShingle | Zhang Z Zhu X Zhang T Li C Zhang D Li W Zhao L Uncovering the Interplay of Ferroptosis and Immune System in Coronary Artery Disease: Construction and Validation of a Diagnostic Model International Journal of General Medicine Coronary artery disease Ferroptosis Immune regulation Biomarkers Disease diagnosis |
| title | Uncovering the Interplay of Ferroptosis and Immune System in Coronary Artery Disease: Construction and Validation of a Diagnostic Model |
| title_full | Uncovering the Interplay of Ferroptosis and Immune System in Coronary Artery Disease: Construction and Validation of a Diagnostic Model |
| title_fullStr | Uncovering the Interplay of Ferroptosis and Immune System in Coronary Artery Disease: Construction and Validation of a Diagnostic Model |
| title_full_unstemmed | Uncovering the Interplay of Ferroptosis and Immune System in Coronary Artery Disease: Construction and Validation of a Diagnostic Model |
| title_short | Uncovering the Interplay of Ferroptosis and Immune System in Coronary Artery Disease: Construction and Validation of a Diagnostic Model |
| title_sort | uncovering the interplay of ferroptosis and immune system in coronary artery disease construction and validation of a diagnostic model |
| topic | Coronary artery disease Ferroptosis Immune regulation Biomarkers Disease diagnosis |
| url | https://www.dovepress.com/uncovering-the-interplay-of-ferroptosis-and-immune-system-in-coronary--peer-reviewed-fulltext-article-IJGM |
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