Six macrophage-associated genes in synovium constitute a novel diagnostic signature for osteoarthritis
BackgroundSynovial macrophages play important roles in the formation and progression of osteoarthritis (OA). This study aimed to explore the biological and clinical significance of macrophage-associated genes (MAGs) in OA.MethodsThe OA synovial gene expression profiles GSE89408 and GSE82107 were obt...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-07-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.936606/full |
| _version_ | 1811311698927157248 |
|---|---|
| author | Yiying Liu Yiying Liu Taoyuan Lu Zaoqu Liu Wenhua Ning Siying Li Siying Li Yanru Chen Yanru Chen Xiaoyong Ge Chunguang Guo Youyang Zheng Xiangyang Wei Haiming Wang Haiming Wang |
| author_facet | Yiying Liu Yiying Liu Taoyuan Lu Zaoqu Liu Wenhua Ning Siying Li Siying Li Yanru Chen Yanru Chen Xiaoyong Ge Chunguang Guo Youyang Zheng Xiangyang Wei Haiming Wang Haiming Wang |
| author_sort | Yiying Liu |
| collection | DOAJ |
| description | BackgroundSynovial macrophages play important roles in the formation and progression of osteoarthritis (OA). This study aimed to explore the biological and clinical significance of macrophage-associated genes (MAGs) in OA.MethodsThe OA synovial gene expression profiles GSE89408 and GSE82107 were obtained from the GEO database. Single-sample gene set enrichment analysis (ssGSEA) and GSEA were employed to decipher differences in immune infiltration and macrophage-associated biological pathways, respectively. Protein–protein interaction (PPI) network analysis and machine learning were utilized to establish a macrophage-associated gene diagnostic signature (MAGDS). RT-qPCR was performed to test the expression of key MAGs in murine models.ResultsOA synovium presented high levels of immune infiltration and activation of macrophage-associated biological pathways. A total of 55 differentially expressed MAGs were identified. Using PPI analysis and machine learning, a MAGDS consisting of IL1B, C5AR1, FCGR2B, IL10, IL6, and TYROBP was established for OA diagnosis (AUC = 0.910) and molecular pathological evaluation. Patients with high MAGDS scores may possess higher levels of immune infiltration and expression of matrix metalloproteinases (MMPs), implying poor biological alterations. The diagnostic value of MAGDS was also validated in an external cohort (AUC = 0.886). The expression of key MAGs was validated in a murine model using RT-qPCR. Additionally, a competitive endogenous RNA network was constructed to reveal the potential posttranscriptional regulatory mechanisms.ConclusionsWe developed and validated a MAGDS model with the ability to accurately diagnose and characterize biological alterations in OA. The six key MAGs may also be latent targets for immunoregulatory therapy. |
| first_indexed | 2024-04-13T10:23:30Z |
| format | Article |
| id | doaj.art-f34f4d9c4f4e48eeae0cda8783aa295e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T10:23:30Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-f34f4d9c4f4e48eeae0cda8783aa295e2022-12-22T02:50:26ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-07-011310.3389/fimmu.2022.936606936606Six macrophage-associated genes in synovium constitute a novel diagnostic signature for osteoarthritisYiying Liu0Yiying Liu1Taoyuan Lu2Zaoqu Liu3Wenhua Ning4Siying Li5Siying Li6Yanru Chen7Yanru Chen8Xiaoyong Ge9Chunguang Guo10Youyang Zheng11Xiangyang Wei12Haiming Wang13Haiming Wang14Academy of Medical Sciences, Zhengzhou University, Zhengzhou, ChinaDepartment of Rehabilitation Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Cerebrovascular Disease, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou, ChinaDepartment of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Rehabilitation Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaAcademy of Medical Sciences, Zhengzhou University, Zhengzhou, ChinaDepartment of Rehabilitation Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaAcademy of Medical Sciences, Zhengzhou University, Zhengzhou, ChinaDepartment of Rehabilitation Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Endovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Cardiovascular Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Rehabilitation Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Rehabilitation Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaMedical College of Zhengzhou University of Industrial technology, Zhengzhou, ChinaBackgroundSynovial macrophages play important roles in the formation and progression of osteoarthritis (OA). This study aimed to explore the biological and clinical significance of macrophage-associated genes (MAGs) in OA.MethodsThe OA synovial gene expression profiles GSE89408 and GSE82107 were obtained from the GEO database. Single-sample gene set enrichment analysis (ssGSEA) and GSEA were employed to decipher differences in immune infiltration and macrophage-associated biological pathways, respectively. Protein–protein interaction (PPI) network analysis and machine learning were utilized to establish a macrophage-associated gene diagnostic signature (MAGDS). RT-qPCR was performed to test the expression of key MAGs in murine models.ResultsOA synovium presented high levels of immune infiltration and activation of macrophage-associated biological pathways. A total of 55 differentially expressed MAGs were identified. Using PPI analysis and machine learning, a MAGDS consisting of IL1B, C5AR1, FCGR2B, IL10, IL6, and TYROBP was established for OA diagnosis (AUC = 0.910) and molecular pathological evaluation. Patients with high MAGDS scores may possess higher levels of immune infiltration and expression of matrix metalloproteinases (MMPs), implying poor biological alterations. The diagnostic value of MAGDS was also validated in an external cohort (AUC = 0.886). The expression of key MAGs was validated in a murine model using RT-qPCR. Additionally, a competitive endogenous RNA network was constructed to reveal the potential posttranscriptional regulatory mechanisms.ConclusionsWe developed and validated a MAGDS model with the ability to accurately diagnose and characterize biological alterations in OA. The six key MAGs may also be latent targets for immunoregulatory therapy.https://www.frontiersin.org/articles/10.3389/fimmu.2022.936606/fullOsteoarthritissynovial macrophagesmacrophage-associated genesmachine learningdiagnostic signatureimmunopathology |
| spellingShingle | Yiying Liu Yiying Liu Taoyuan Lu Zaoqu Liu Wenhua Ning Siying Li Siying Li Yanru Chen Yanru Chen Xiaoyong Ge Chunguang Guo Youyang Zheng Xiangyang Wei Haiming Wang Haiming Wang Six macrophage-associated genes in synovium constitute a novel diagnostic signature for osteoarthritis Frontiers in Immunology Osteoarthritis synovial macrophages macrophage-associated genes machine learning diagnostic signature immunopathology |
| title | Six macrophage-associated genes in synovium constitute a novel diagnostic signature for osteoarthritis |
| title_full | Six macrophage-associated genes in synovium constitute a novel diagnostic signature for osteoarthritis |
| title_fullStr | Six macrophage-associated genes in synovium constitute a novel diagnostic signature for osteoarthritis |
| title_full_unstemmed | Six macrophage-associated genes in synovium constitute a novel diagnostic signature for osteoarthritis |
| title_short | Six macrophage-associated genes in synovium constitute a novel diagnostic signature for osteoarthritis |
| title_sort | six macrophage associated genes in synovium constitute a novel diagnostic signature for osteoarthritis |
| topic | Osteoarthritis synovial macrophages macrophage-associated genes machine learning diagnostic signature immunopathology |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.936606/full |
| work_keys_str_mv | AT yiyingliu sixmacrophageassociatedgenesinsynoviumconstituteanoveldiagnosticsignatureforosteoarthritis AT yiyingliu sixmacrophageassociatedgenesinsynoviumconstituteanoveldiagnosticsignatureforosteoarthritis AT taoyuanlu sixmacrophageassociatedgenesinsynoviumconstituteanoveldiagnosticsignatureforosteoarthritis AT zaoquliu sixmacrophageassociatedgenesinsynoviumconstituteanoveldiagnosticsignatureforosteoarthritis AT wenhuaning sixmacrophageassociatedgenesinsynoviumconstituteanoveldiagnosticsignatureforosteoarthritis AT siyingli sixmacrophageassociatedgenesinsynoviumconstituteanoveldiagnosticsignatureforosteoarthritis AT siyingli sixmacrophageassociatedgenesinsynoviumconstituteanoveldiagnosticsignatureforosteoarthritis AT yanruchen sixmacrophageassociatedgenesinsynoviumconstituteanoveldiagnosticsignatureforosteoarthritis AT yanruchen sixmacrophageassociatedgenesinsynoviumconstituteanoveldiagnosticsignatureforosteoarthritis AT xiaoyongge sixmacrophageassociatedgenesinsynoviumconstituteanoveldiagnosticsignatureforosteoarthritis AT chunguangguo sixmacrophageassociatedgenesinsynoviumconstituteanoveldiagnosticsignatureforosteoarthritis AT youyangzheng sixmacrophageassociatedgenesinsynoviumconstituteanoveldiagnosticsignatureforosteoarthritis AT xiangyangwei sixmacrophageassociatedgenesinsynoviumconstituteanoveldiagnosticsignatureforosteoarthritis AT haimingwang sixmacrophageassociatedgenesinsynoviumconstituteanoveldiagnosticsignatureforosteoarthritis AT haimingwang sixmacrophageassociatedgenesinsynoviumconstituteanoveldiagnosticsignatureforosteoarthritis |