Identification of Hub Biomarkers and Immune and Inflammation Pathways Contributing to Kawasaki Disease Progression with RT-qPCR Verification
Background. Kawasaki disease (KD) is characterized by a disordered inflammation response of unknown etiology. Immune cells are closely associated with its onset, although the immune-related genes’ expression and possibly involved immune regulatory mechanisms are little known. This study aims to iden...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Hindawi Limited
2023-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2023/1774260 |
| _version_ | 1797847354009714688 |
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| author | Hongjun Ba Lili Zhang Huimin Peng Xiufang He Yuese Lin Xuandi Li Shujuan Li Ling Zhu Youzhen Qin Xing Zhang Yao Wang |
| author_facet | Hongjun Ba Lili Zhang Huimin Peng Xiufang He Yuese Lin Xuandi Li Shujuan Li Ling Zhu Youzhen Qin Xing Zhang Yao Wang |
| author_sort | Hongjun Ba |
| collection | DOAJ |
| description | Background. Kawasaki disease (KD) is characterized by a disordered inflammation response of unknown etiology. Immune cells are closely associated with its onset, although the immune-related genes’ expression and possibly involved immune regulatory mechanisms are little known. This study aims to identify KD-implicated significant immune- and inflammation-related biomarkers and pathways and their association with immune cell infiltration. Patients and Methods. Gene microarray data were collected from the Gene Expression Omnibus database. Differential expression analysis, weighted gene coexpression network analysis (WGCNA), least absolute shrinkage and selection operator (LASSO) regression, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were used to find KD hub markers. GSEA was used to assess the infiltration by 28 immune cell types and their connections to essential gene markers. Receiver operating characteristic (ROC) curves were used to examine hub markers’ diagnostic effectiveness. Finally, hub genes’ expressions were validated in Chinese KD patients by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results. One hundred and fifty-one unique genes were found. Among 10 coexpression modules at WGCNA, one hub module exhibited the strongest association with KD. Thirty-six overlapping genes were identified. Six hub genes were potential biomarkers according to LASSO analysis. Immune infiltration revealed connections among activated and effector memory CD4+ T cells, neutrophils, activated dendritic cells, and macrophages. The six hub genes’ diagnostic value was shown by ROC curve analysis. Hub genes were enriched in immunological and inflammatory pathways. RT-qPCR verification results of FCGR1B (P<0.001), GPR84 (P<0.001), KREMEN1 (P<0.001), LRG1 (P<0.001), and TDRD9 (P<0.001) upregulated expression in Chinese KD patients are consistent with our database analysis. Conclusion. Neutrophils, macrophages, and activated dendritic cells are strongly linked to KD pathophysiology. Through immune-related signaling pathways, hub genes such as FCGR1B, GPR84, KREMEN1, LRG1, and TDRD9 may be implicated in KD advancement. |
| first_indexed | 2024-04-09T18:10:01Z |
| format | Article |
| id | doaj.art-5dd7a1ea788c44d587ada593185f0f49 |
| institution | Directory Open Access Journal |
| issn | 2314-7156 |
| language | English |
| last_indexed | 2024-04-09T18:10:01Z |
| publishDate | 2023-01-01 |
| publisher | Hindawi Limited |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj.art-5dd7a1ea788c44d587ada593185f0f492023-04-14T00:00:08ZengHindawi LimitedJournal of Immunology Research2314-71562023-01-01202310.1155/2023/1774260Identification of Hub Biomarkers and Immune and Inflammation Pathways Contributing to Kawasaki Disease Progression with RT-qPCR VerificationHongjun Ba0Lili Zhang1Huimin Peng2Xiufang He3Yuese Lin4Xuandi Li5Shujuan Li6Ling Zhu7Youzhen Qin8Xing Zhang9Yao Wang10Department of Pediatric CardiologyDepartment of Pediatric CardiologyDepartment of Pediatric CardiologyDepartment of Pediatric CardiologyDepartment of Pediatric CardiologyDepartment of Pediatric CardiologyDepartment of Pediatric CardiologyDepartment of Pediatric CardiologyDepartment of Pediatric CardiologyDepartment of CardiologyCancer HospitalBackground. Kawasaki disease (KD) is characterized by a disordered inflammation response of unknown etiology. Immune cells are closely associated with its onset, although the immune-related genes’ expression and possibly involved immune regulatory mechanisms are little known. This study aims to identify KD-implicated significant immune- and inflammation-related biomarkers and pathways and their association with immune cell infiltration. Patients and Methods. Gene microarray data were collected from the Gene Expression Omnibus database. Differential expression analysis, weighted gene coexpression network analysis (WGCNA), least absolute shrinkage and selection operator (LASSO) regression, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were used to find KD hub markers. GSEA was used to assess the infiltration by 28 immune cell types and their connections to essential gene markers. Receiver operating characteristic (ROC) curves were used to examine hub markers’ diagnostic effectiveness. Finally, hub genes’ expressions were validated in Chinese KD patients by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results. One hundred and fifty-one unique genes were found. Among 10 coexpression modules at WGCNA, one hub module exhibited the strongest association with KD. Thirty-six overlapping genes were identified. Six hub genes were potential biomarkers according to LASSO analysis. Immune infiltration revealed connections among activated and effector memory CD4+ T cells, neutrophils, activated dendritic cells, and macrophages. The six hub genes’ diagnostic value was shown by ROC curve analysis. Hub genes were enriched in immunological and inflammatory pathways. RT-qPCR verification results of FCGR1B (P<0.001), GPR84 (P<0.001), KREMEN1 (P<0.001), LRG1 (P<0.001), and TDRD9 (P<0.001) upregulated expression in Chinese KD patients are consistent with our database analysis. Conclusion. Neutrophils, macrophages, and activated dendritic cells are strongly linked to KD pathophysiology. Through immune-related signaling pathways, hub genes such as FCGR1B, GPR84, KREMEN1, LRG1, and TDRD9 may be implicated in KD advancement.http://dx.doi.org/10.1155/2023/1774260 |
| spellingShingle | Hongjun Ba Lili Zhang Huimin Peng Xiufang He Yuese Lin Xuandi Li Shujuan Li Ling Zhu Youzhen Qin Xing Zhang Yao Wang Identification of Hub Biomarkers and Immune and Inflammation Pathways Contributing to Kawasaki Disease Progression with RT-qPCR Verification Journal of Immunology Research |
| title | Identification of Hub Biomarkers and Immune and Inflammation Pathways Contributing to Kawasaki Disease Progression with RT-qPCR Verification |
| title_full | Identification of Hub Biomarkers and Immune and Inflammation Pathways Contributing to Kawasaki Disease Progression with RT-qPCR Verification |
| title_fullStr | Identification of Hub Biomarkers and Immune and Inflammation Pathways Contributing to Kawasaki Disease Progression with RT-qPCR Verification |
| title_full_unstemmed | Identification of Hub Biomarkers and Immune and Inflammation Pathways Contributing to Kawasaki Disease Progression with RT-qPCR Verification |
| title_short | Identification of Hub Biomarkers and Immune and Inflammation Pathways Contributing to Kawasaki Disease Progression with RT-qPCR Verification |
| title_sort | identification of hub biomarkers and immune and inflammation pathways contributing to kawasaki disease progression with rt qpcr verification |
| url | http://dx.doi.org/10.1155/2023/1774260 |
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