Identification of Hub Biomarkers and Immune-Related Pathways Participating in the Progression of Antineutrophil Cytoplasmic Antibody-Associated Glomerulonephritis
BackgroundAntineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic autoimmune disease that generally induces the progression of rapidly progressive glomerulonephritis (GN). The purpose of this study was to identify key biomarkers and immune-related pathways involved in th...
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.809325/full |
| _version_ | 1798034242874114048 |
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| author | Meng-Di Xia Meng-Di Xia Rui-Ran Yu Dong-Ming Chen Dong-Ming Chen |
| author_facet | Meng-Di Xia Meng-Di Xia Rui-Ran Yu Dong-Ming Chen Dong-Ming Chen |
| author_sort | Meng-Di Xia |
| collection | DOAJ |
| description | BackgroundAntineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic autoimmune disease that generally induces the progression of rapidly progressive glomerulonephritis (GN). The purpose of this study was to identify key biomarkers and immune-related pathways involved in the progression of ANCA-associated GN (ANCA-GN) and their relationship with immune cell infiltration.MethodsGene microarray data were downloaded from the Gene Expression Omnibus (GEO). Hub markers for ANCA-GN were mined based on differential expression analysis, weighted gene co-expression network analysis (WGCNA) and lasso regression, followed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) of the differential genes. The infiltration levels of 28 immune cells in the expression profile and their relationship to hub gene markers were analysed using single-sample GSEA (ssGSEA). In addition, the accuracy of the hub markers in diagnosing ANCA-GN was subsequently evaluated using the receiver operating characteristic curve (ROC).ResultsA total of 651 differential genes were screened. Twelve co-expression modules were obtained via WGCNA; of which, one hub module (black module) had the highest correlation with ANCA-GN. A total of 66 intersecting genes were acquired by combining differential genes. Five hub genes were subsequently obtained by lasso analysis as potential biomarkers for ANCA-GN. The immune infiltration results revealed the most significant relationship among monocytes, CD4+ T cells and CD8+ T cells. ROC curve analysis demonstrated a prime diagnostic value of the five hub genes. According to the functional enrichment analysis of the differential genes, hub genes were mainly enhanced in immune- and inflammation-related pathways.ConclusionB cells and monocytes were closely associated with the pathogenesis of ANCA-GN. Hub genes (CYP3A5, SLC12A3, BGN, TAPBP and TMEM184B) may be involved in the progression of ANCA-GN through immune-related signal pathways. |
| first_indexed | 2024-04-11T20:41:40Z |
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| id | doaj.art-68735795cd0244ff818199f6fd40cb3c |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T20:41:40Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-68735795cd0244ff818199f6fd40cb3c2022-12-22T04:04:11ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-01-011210.3389/fimmu.2021.809325809325Identification of Hub Biomarkers and Immune-Related Pathways Participating in the Progression of Antineutrophil Cytoplasmic Antibody-Associated GlomerulonephritisMeng-Di Xia0Meng-Di Xia1Rui-Ran Yu2Dong-Ming Chen3Dong-Ming Chen4Department of Nephrology, The Second Clinical Medical Institution of North Sichuan Medical College (Nanchong Central Hospital) and Nanchong Key Laboratory of Basic Science & Clinical Research on Chronic Kidney Disease, Nanchong, ChinaDepartment of Nephrology and Medical Intensive Care, Charité – Universtitätsmedizin Berlin, Cooperate Member of Freie Universität and Humboldt Universität, Hindenburgdamm, Berlin, GermanyDepartment of Oncology, Anqing First People’s Hospital of Anhui Medical University, Anqing, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, ChinaCharité – Universtitätsmedizin Berlin, Cooperate Member of Freie Universität and Humboldt Universität, Berlin, GermanyBackgroundAntineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic autoimmune disease that generally induces the progression of rapidly progressive glomerulonephritis (GN). The purpose of this study was to identify key biomarkers and immune-related pathways involved in the progression of ANCA-associated GN (ANCA-GN) and their relationship with immune cell infiltration.MethodsGene microarray data were downloaded from the Gene Expression Omnibus (GEO). Hub markers for ANCA-GN were mined based on differential expression analysis, weighted gene co-expression network analysis (WGCNA) and lasso regression, followed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) of the differential genes. The infiltration levels of 28 immune cells in the expression profile and their relationship to hub gene markers were analysed using single-sample GSEA (ssGSEA). In addition, the accuracy of the hub markers in diagnosing ANCA-GN was subsequently evaluated using the receiver operating characteristic curve (ROC).ResultsA total of 651 differential genes were screened. Twelve co-expression modules were obtained via WGCNA; of which, one hub module (black module) had the highest correlation with ANCA-GN. A total of 66 intersecting genes were acquired by combining differential genes. Five hub genes were subsequently obtained by lasso analysis as potential biomarkers for ANCA-GN. The immune infiltration results revealed the most significant relationship among monocytes, CD4+ T cells and CD8+ T cells. ROC curve analysis demonstrated a prime diagnostic value of the five hub genes. According to the functional enrichment analysis of the differential genes, hub genes were mainly enhanced in immune- and inflammation-related pathways.ConclusionB cells and monocytes were closely associated with the pathogenesis of ANCA-GN. Hub genes (CYP3A5, SLC12A3, BGN, TAPBP and TMEM184B) may be involved in the progression of ANCA-GN through immune-related signal pathways.https://www.frontiersin.org/articles/10.3389/fimmu.2021.809325/fullantineutrophil cytoplasmic antibody-associated vasculitisbiomarkerimmune cell infiltrationLASSOweighted gene co-expression network analysisimmune-related pathways |
| spellingShingle | Meng-Di Xia Meng-Di Xia Rui-Ran Yu Dong-Ming Chen Dong-Ming Chen Identification of Hub Biomarkers and Immune-Related Pathways Participating in the Progression of Antineutrophil Cytoplasmic Antibody-Associated Glomerulonephritis Frontiers in Immunology antineutrophil cytoplasmic antibody-associated vasculitis biomarker immune cell infiltration LASSO weighted gene co-expression network analysis immune-related pathways |
| title | Identification of Hub Biomarkers and Immune-Related Pathways Participating in the Progression of Antineutrophil Cytoplasmic Antibody-Associated Glomerulonephritis |
| title_full | Identification of Hub Biomarkers and Immune-Related Pathways Participating in the Progression of Antineutrophil Cytoplasmic Antibody-Associated Glomerulonephritis |
| title_fullStr | Identification of Hub Biomarkers and Immune-Related Pathways Participating in the Progression of Antineutrophil Cytoplasmic Antibody-Associated Glomerulonephritis |
| title_full_unstemmed | Identification of Hub Biomarkers and Immune-Related Pathways Participating in the Progression of Antineutrophil Cytoplasmic Antibody-Associated Glomerulonephritis |
| title_short | Identification of Hub Biomarkers and Immune-Related Pathways Participating in the Progression of Antineutrophil Cytoplasmic Antibody-Associated Glomerulonephritis |
| title_sort | identification of hub biomarkers and immune related pathways participating in the progression of antineutrophil cytoplasmic antibody associated glomerulonephritis |
| topic | antineutrophil cytoplasmic antibody-associated vasculitis biomarker immune cell infiltration LASSO weighted gene co-expression network analysis immune-related pathways |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.809325/full |
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