Identification of key genes and the pathophysiology associated with allergen-specific immunotherapy for allergic rhinitis
Abstract Background Allergen-specific immunotherapy (AIT) is a causative treatment in allergic rhinitis (AR), comprising long-term allergen administration and over three years of treatment. This study is carried out for revealing the mechanisms and key genes of AIT in AR. Methods The present study u...
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| Format: | Article |
| Language: | English |
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BMC
2023-07-01
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| Series: | BMC Immunology |
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| Online Access: | https://doi.org/10.1186/s12865-023-00556-1 |
| _version_ | 1797778965289500672 |
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| author | Kai Fan Shican Zhou Ling Jin Shiwang Tan Ju Lai Zimu Zhang Jingwen Li Xiayue Xu Chunyan Yao Zhiqiang Yan Shaoqing Yu |
| author_facet | Kai Fan Shican Zhou Ling Jin Shiwang Tan Ju Lai Zimu Zhang Jingwen Li Xiayue Xu Chunyan Yao Zhiqiang Yan Shaoqing Yu |
| author_sort | Kai Fan |
| collection | DOAJ |
| description | Abstract Background Allergen-specific immunotherapy (AIT) is a causative treatment in allergic rhinitis (AR), comprising long-term allergen administration and over three years of treatment. This study is carried out for revealing the mechanisms and key genes of AIT in AR. Methods The present study utilized online Gene Expression Omnibus (GEO) microarray expression profiling dataset GSE37157 and GSE29521 to analyze the hub genes changes related to AIT in AR. Based on limma package, differential expression analysis for the two groups (samples of allergic patients prior to AIT and samples of allergic patients undergoing AIT) was performed to obtain differentially expressed genes (DEGs). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEGs were conducted using DAVID database. A Protein-Protein Interaction network (PPI) was built and a significant network module was acquired by using Cytoscape software (Cytoscape, 3.7.2). Utilizing the miRWalk database, we identified potential gene biomarkers, constructed interaction networks of target genes and microRNAs (miRNAs) using Cytoscape software, and explore the cell type-specific expression patterns of these genes in peripheral blood using publicly available single-cell RNA sequencing data (GSE200107). Finally, we are using PCR to detect changes in the hub genes that are screened using the above method in peripheral blood before and after AIT treatment. Results GSE37157 and GSE29521 included 28 and 13 samples, respectively. A total of 119 significantly co-upregulated DEGs and 33 co-downregulated DEGs were obtained from two datasets. The GO and KEGG analyses demonstrated that protein transport, positive regulation of apoptotic process, Natural killer cell mediated cytotoxicity, T cell receptor signaling pathway, TNF signaling pathway, B cell receptor signaling pathway and Apoptosis may be potential candidate therapeutic targets for AIT of AR. From the PPI network, 20 hub genes were obtained. Among them, the PPI sub-networks of CASP3, FOXO3, PIK3R1, PIK3R3, ATF4, and POLD3 screened out from our study have been identified as reliable predictors of AIT in AR, especially the PIK3R1. Conclusion Our analysis has identified novel gene signatures, thereby contributing to a more comprehensive understanding of the molecular mechanisms underlying AIT in the treatment of AR. |
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| id | doaj.art-5253ae399c4745969bdcadf431fbc6a0 |
| institution | Directory Open Access Journal |
| issn | 1471-2172 |
| language | English |
| last_indexed | 2024-03-12T23:24:11Z |
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| spelling | doaj.art-5253ae399c4745969bdcadf431fbc6a02023-07-16T11:13:32ZengBMCBMC Immunology1471-21722023-07-0124111010.1186/s12865-023-00556-1Identification of key genes and the pathophysiology associated with allergen-specific immunotherapy for allergic rhinitisKai Fan0Shican Zhou1Ling Jin2Shiwang Tan3Ju Lai4Zimu Zhang5Jingwen Li6Xiayue Xu7Chunyan Yao8Zhiqiang Yan9Shaoqing Yu10Department of Otorhinolaryngology-Head and Neck Surgery, Tongji Hospital, School of Medicine, Tongji UniversityDepartment of Otorhinolaryngology-Head and Neck Surgery, Tongji Hospital, School of Medicine, Tongji UniversityDepartment of Otorhinolaryngology-Head and Neck Surgery, Tongji Hospital, School of Medicine, Tongji UniversityDepartment of Otorhinolaryngology-Head and Neck Surgery, Tongji Hospital, School of Medicine, Tongji UniversityDepartment of Otorhinolaryngology-Head and Neck Surgery, Tongji Hospital, School of Medicine, Tongji UniversityDepartment of Otorhinolaryngology-Head and Neck Surgery, Tongji Hospital, School of Medicine, Tongji UniversityDepartment of Otorhinolaryngology-Head and Neck Surgery, Tongji Hospital, School of Medicine, Tongji UniversityDepartment of Otorhinolaryngology-Head and Neck Surgery, Tongji Hospital, School of Medicine, Tongji UniversityDepartment of Otorhinolaryngology-Head and Neck Surgery, Tongji Hospital, School of Medicine, Tongji UniversityDepartment of Otolaryngology Head & Neck Surgery, The Affilicated Huaihai Hospital of Xuzhou Medical UniversityDepartment of Otorhinolaryngology-Head and Neck Surgery, Tongji Hospital, School of Medicine, Tongji UniversityAbstract Background Allergen-specific immunotherapy (AIT) is a causative treatment in allergic rhinitis (AR), comprising long-term allergen administration and over three years of treatment. This study is carried out for revealing the mechanisms and key genes of AIT in AR. Methods The present study utilized online Gene Expression Omnibus (GEO) microarray expression profiling dataset GSE37157 and GSE29521 to analyze the hub genes changes related to AIT in AR. Based on limma package, differential expression analysis for the two groups (samples of allergic patients prior to AIT and samples of allergic patients undergoing AIT) was performed to obtain differentially expressed genes (DEGs). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEGs were conducted using DAVID database. A Protein-Protein Interaction network (PPI) was built and a significant network module was acquired by using Cytoscape software (Cytoscape, 3.7.2). Utilizing the miRWalk database, we identified potential gene biomarkers, constructed interaction networks of target genes and microRNAs (miRNAs) using Cytoscape software, and explore the cell type-specific expression patterns of these genes in peripheral blood using publicly available single-cell RNA sequencing data (GSE200107). Finally, we are using PCR to detect changes in the hub genes that are screened using the above method in peripheral blood before and after AIT treatment. Results GSE37157 and GSE29521 included 28 and 13 samples, respectively. A total of 119 significantly co-upregulated DEGs and 33 co-downregulated DEGs were obtained from two datasets. The GO and KEGG analyses demonstrated that protein transport, positive regulation of apoptotic process, Natural killer cell mediated cytotoxicity, T cell receptor signaling pathway, TNF signaling pathway, B cell receptor signaling pathway and Apoptosis may be potential candidate therapeutic targets for AIT of AR. From the PPI network, 20 hub genes were obtained. Among them, the PPI sub-networks of CASP3, FOXO3, PIK3R1, PIK3R3, ATF4, and POLD3 screened out from our study have been identified as reliable predictors of AIT in AR, especially the PIK3R1. Conclusion Our analysis has identified novel gene signatures, thereby contributing to a more comprehensive understanding of the molecular mechanisms underlying AIT in the treatment of AR.https://doi.org/10.1186/s12865-023-00556-1Allergen-specific immunotherapyAllergic rhinitisBioinformatics analysisDifferentially expressed genesmicroRNAs. |
| spellingShingle | Kai Fan Shican Zhou Ling Jin Shiwang Tan Ju Lai Zimu Zhang Jingwen Li Xiayue Xu Chunyan Yao Zhiqiang Yan Shaoqing Yu Identification of key genes and the pathophysiology associated with allergen-specific immunotherapy for allergic rhinitis BMC Immunology Allergen-specific immunotherapy Allergic rhinitis Bioinformatics analysis Differentially expressed genes microRNAs. |
| title | Identification of key genes and the pathophysiology associated with allergen-specific immunotherapy for allergic rhinitis |
| title_full | Identification of key genes and the pathophysiology associated with allergen-specific immunotherapy for allergic rhinitis |
| title_fullStr | Identification of key genes and the pathophysiology associated with allergen-specific immunotherapy for allergic rhinitis |
| title_full_unstemmed | Identification of key genes and the pathophysiology associated with allergen-specific immunotherapy for allergic rhinitis |
| title_short | Identification of key genes and the pathophysiology associated with allergen-specific immunotherapy for allergic rhinitis |
| title_sort | identification of key genes and the pathophysiology associated with allergen specific immunotherapy for allergic rhinitis |
| topic | Allergen-specific immunotherapy Allergic rhinitis Bioinformatics analysis Differentially expressed genes microRNAs. |
| url | https://doi.org/10.1186/s12865-023-00556-1 |
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