Angiogenesis-related genes and immune microenvironment in moyamoya disease: a transcriptomic and functional analysis
Abstract Background Moyamoya disease (MMD) is a chronic, progressive occlusive cerebrovascular disease. It causes recurrent cerebrovascular stroke due to vascular closure and proliferation. An unclear pathophysiological mechanism is the most significant obstacle in the diagnosis and treatment of MMD...
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BMC
2025-07-01
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| Series: | Orphanet Journal of Rare Diseases |
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| Online Access: | https://doi.org/10.1186/s13023-025-03945-4 |
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| author | Zhenyu Zhou Hongchuan Niu Shaoqi Xu Junze Zhang Yutong Liu Chengxu Lei Shihao He Yuanli Zhao |
| author_facet | Zhenyu Zhou Hongchuan Niu Shaoqi Xu Junze Zhang Yutong Liu Chengxu Lei Shihao He Yuanli Zhao |
| author_sort | Zhenyu Zhou |
| collection | DOAJ |
| description | Abstract Background Moyamoya disease (MMD) is a chronic, progressive occlusive cerebrovascular disease. It causes recurrent cerebrovascular stroke due to vascular closure and proliferation. An unclear pathophysiological mechanism is the most significant obstacle in the diagnosis and treatment of MMD. Method This study prospectively included 10 MMD and 3 HC (healthy controls) participants in the discovery cohort. GSE189993 and GSE157628 were downloaded from the Gene Expression Omnibus (GEO) as validation cohorts, which included 32 patients with MMD and 20 HC. Angiogenesis-related genes were downloaded from GENECARD. Hub genes were selected by differential analysis and weighted correlation network analysis. Functional enrichment, immune infiltration, and metabolic pathway analyses and drug prediction mapping (Connectivity Map [CMap]) were performed. Result Through differential analysis identified, 198 differentially expressed genes (DEGs), including 85 upregulated genes and 113 downregulated genes. In total, 238 angiogenesis -related genes were identified using WGCNA. Four hub genes were identified: TBC1 domain family member 9B (TBC1D9B), Phosphatidylinositol transfer protein beta (PITPNB), The ANK repeat and PH domain-containing protein 3 (ARAP3), and Ubiquitin-conjugating enzyme E2 E1 (UBE2E1). Four potential drugs were selected: calyculin A, H-9, parbendazole, and velnacrine. The results of multiple immune infiltration analyses collectively depicted the immune microenvironment characteristics of MMD. Conclusion This study is the first to explore the mechanism by which angiogenesis related genes are involved in intimal hyperplasia in Moyamoya disease. TBC1D9B and ARAP3 may promote the pathological development of moyamoya disease through immune response, metabolism. |
| format | Article |
| id | doaj-art-3e3d05fc8ecc4223af76a494e6ecfd11 |
| institution | DOAJ |
| issn | 1750-1172 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj-art-3e3d05fc8ecc4223af76a494e6ecfd112025-08-20T03:06:05ZengBMCOrphanet Journal of Rare Diseases1750-11722025-07-0120111710.1186/s13023-025-03945-4Angiogenesis-related genes and immune microenvironment in moyamoya disease: a transcriptomic and functional analysisZhenyu Zhou0Hongchuan Niu1Shaoqi Xu2Junze Zhang3Yutong Liu4Chengxu Lei5Shihao He6Yuanli Zhao7Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Neurosurgery, Peking University International HospitalSuzhou Vocational Health CollegeDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Neurosurgery, Peking Union Medical College and Chinese Academy of Medical Sciences, Peking Union Medical College HospitalDepartment of Neurosurgery, Peking Union Medical College and Chinese Academy of Medical Sciences, Peking Union Medical College HospitalDepartment of Neurosurgery, Peking Union Medical College and Chinese Academy of Medical Sciences, Peking Union Medical College HospitalDepartment of Neurosurgery, Peking Union Medical College and Chinese Academy of Medical Sciences, Peking Union Medical College HospitalAbstract Background Moyamoya disease (MMD) is a chronic, progressive occlusive cerebrovascular disease. It causes recurrent cerebrovascular stroke due to vascular closure and proliferation. An unclear pathophysiological mechanism is the most significant obstacle in the diagnosis and treatment of MMD. Method This study prospectively included 10 MMD and 3 HC (healthy controls) participants in the discovery cohort. GSE189993 and GSE157628 were downloaded from the Gene Expression Omnibus (GEO) as validation cohorts, which included 32 patients with MMD and 20 HC. Angiogenesis-related genes were downloaded from GENECARD. Hub genes were selected by differential analysis and weighted correlation network analysis. Functional enrichment, immune infiltration, and metabolic pathway analyses and drug prediction mapping (Connectivity Map [CMap]) were performed. Result Through differential analysis identified, 198 differentially expressed genes (DEGs), including 85 upregulated genes and 113 downregulated genes. In total, 238 angiogenesis -related genes were identified using WGCNA. Four hub genes were identified: TBC1 domain family member 9B (TBC1D9B), Phosphatidylinositol transfer protein beta (PITPNB), The ANK repeat and PH domain-containing protein 3 (ARAP3), and Ubiquitin-conjugating enzyme E2 E1 (UBE2E1). Four potential drugs were selected: calyculin A, H-9, parbendazole, and velnacrine. The results of multiple immune infiltration analyses collectively depicted the immune microenvironment characteristics of MMD. Conclusion This study is the first to explore the mechanism by which angiogenesis related genes are involved in intimal hyperplasia in Moyamoya disease. TBC1D9B and ARAP3 may promote the pathological development of moyamoya disease through immune response, metabolism.https://doi.org/10.1186/s13023-025-03945-4Moyamoya diseaseAngiogenesisImmuneMulti-omics |
| spellingShingle | Zhenyu Zhou Hongchuan Niu Shaoqi Xu Junze Zhang Yutong Liu Chengxu Lei Shihao He Yuanli Zhao Angiogenesis-related genes and immune microenvironment in moyamoya disease: a transcriptomic and functional analysis Orphanet Journal of Rare Diseases Moyamoya disease Angiogenesis Immune Multi-omics |
| title | Angiogenesis-related genes and immune microenvironment in moyamoya disease: a transcriptomic and functional analysis |
| title_full | Angiogenesis-related genes and immune microenvironment in moyamoya disease: a transcriptomic and functional analysis |
| title_fullStr | Angiogenesis-related genes and immune microenvironment in moyamoya disease: a transcriptomic and functional analysis |
| title_full_unstemmed | Angiogenesis-related genes and immune microenvironment in moyamoya disease: a transcriptomic and functional analysis |
| title_short | Angiogenesis-related genes and immune microenvironment in moyamoya disease: a transcriptomic and functional analysis |
| title_sort | angiogenesis related genes and immune microenvironment in moyamoya disease a transcriptomic and functional analysis |
| topic | Moyamoya disease Angiogenesis Immune Multi-omics |
| url | https://doi.org/10.1186/s13023-025-03945-4 |
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