Integrated bioinformatics analysis for identifying fibroblast-associated biomarkers and molecular subtypes in human membranous nephropathy
Background: Membranous nephropathy (MN) is characterized by immune complex deposition in the glomerular basement membrane, leading to proteinuria and potentially progressive renal dysfunction. Fibroblasts have been implicated in the pathogenesis of MN through their involvement in tissue remodeling a...
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Elsevier
2024-11-01
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| author | Chuying Gui Sidi Liu Zhike Fu Huijie Li Di Zhang Yueyi Deng |
| author_facet | Chuying Gui Sidi Liu Zhike Fu Huijie Li Di Zhang Yueyi Deng |
| author_sort | Chuying Gui |
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| description | Background: Membranous nephropathy (MN) is characterized by immune complex deposition in the glomerular basement membrane, leading to proteinuria and potentially progressive renal dysfunction. Fibroblasts have been implicated in the pathogenesis of MN through their involvement in tissue remodeling and immune modulation. Methods: We employed integrated bioinformatics analyses to identify fibroblast-associated biomarkers and molecular subtypes in MN. The xCell algorithm was used to assess fibroblast infiltration, and weighted gene co-expression network analysis (WGCNA) identified fibroblast-related gene modules. Differentially expressed fibroblast-associated genes (DEFAGs) were screened between MN and healthy controls (HC) using differential expression analysis and protein-protein interaction (PPI) network construction. Consensus clustering categorized MN patients into distinct subtypes based on DEFAG expression profiles. Results: Fibroblast scores were a significant elevation in MN compared to HC, indicating increased fibroblast involvement in MN pathogenesis. WGCNA identified 13 fibroblast-related gene modules, with the brown and turquoise modules showing strong correlation with fibroblast scores (correlation coefficient = 0.79 and 0.75, respectively, p < 0.01). DEFAG analysis revealed 308 genes overlapping between WGCNA and differentially expressed genes (DEGs) in MN. Consensus clustering identified two molecular subtypes (C1 and C2) based on DEFAG expression patterns, with differential gene expression enriching pathways related to immune response and extracellular matrix remodeling. Core biomarker analysis highlighted COL3A1 and TGFB1 as central genes associated with MN, with elevated expression validated across multiple datasets. Conclusion: Integrated bioinformatics analysis identified fibroblast-associated molecular subtypes in MN, revealing distinct immune profiles and biomarkers. COL3A1 emerged as a potential diagnostic and therapeutic target, implicating its role in immune regulation and disease progression in MN. |
| format | Article |
| id | doaj-art-b31ebc177cad42a9b5b52e2f0c0e40d9 |
| institution | Kabale University |
| issn | 2405-8440 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj-art-b31ebc177cad42a9b5b52e2f0c0e40d92024-11-15T06:12:19ZengElsevierHeliyon2405-84402024-11-011021e38424Integrated bioinformatics analysis for identifying fibroblast-associated biomarkers and molecular subtypes in human membranous nephropathyChuying Gui0Sidi Liu1Zhike Fu2Huijie Li3Di Zhang4Yueyi Deng5Corresponding author. The Department of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, NO.725, South Wanping Road, Xuhui District, Shanghai, 200032, China.; The Department of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, ChinaThe Department of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, ChinaThe Department of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, ChinaThe Department of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, ChinaThe Department of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, ChinaCorresponding author. The Department of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, NO.725, South Wanping Road, Xuhui District, Shanghai, 200032, China.; The Department of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, ChinaBackground: Membranous nephropathy (MN) is characterized by immune complex deposition in the glomerular basement membrane, leading to proteinuria and potentially progressive renal dysfunction. Fibroblasts have been implicated in the pathogenesis of MN through their involvement in tissue remodeling and immune modulation. Methods: We employed integrated bioinformatics analyses to identify fibroblast-associated biomarkers and molecular subtypes in MN. The xCell algorithm was used to assess fibroblast infiltration, and weighted gene co-expression network analysis (WGCNA) identified fibroblast-related gene modules. Differentially expressed fibroblast-associated genes (DEFAGs) were screened between MN and healthy controls (HC) using differential expression analysis and protein-protein interaction (PPI) network construction. Consensus clustering categorized MN patients into distinct subtypes based on DEFAG expression profiles. Results: Fibroblast scores were a significant elevation in MN compared to HC, indicating increased fibroblast involvement in MN pathogenesis. WGCNA identified 13 fibroblast-related gene modules, with the brown and turquoise modules showing strong correlation with fibroblast scores (correlation coefficient = 0.79 and 0.75, respectively, p < 0.01). DEFAG analysis revealed 308 genes overlapping between WGCNA and differentially expressed genes (DEGs) in MN. Consensus clustering identified two molecular subtypes (C1 and C2) based on DEFAG expression patterns, with differential gene expression enriching pathways related to immune response and extracellular matrix remodeling. Core biomarker analysis highlighted COL3A1 and TGFB1 as central genes associated with MN, with elevated expression validated across multiple datasets. Conclusion: Integrated bioinformatics analysis identified fibroblast-associated molecular subtypes in MN, revealing distinct immune profiles and biomarkers. COL3A1 emerged as a potential diagnostic and therapeutic target, implicating its role in immune regulation and disease progression in MN.http://www.sciencedirect.com/science/article/pii/S2405844024144556Membranous nephropathyFibroblastsBiomarkersMolecular subtypesIntegrated bioinformatics |
| spellingShingle | Chuying Gui Sidi Liu Zhike Fu Huijie Li Di Zhang Yueyi Deng Integrated bioinformatics analysis for identifying fibroblast-associated biomarkers and molecular subtypes in human membranous nephropathy Heliyon Membranous nephropathy Fibroblasts Biomarkers Molecular subtypes Integrated bioinformatics |
| title | Integrated bioinformatics analysis for identifying fibroblast-associated biomarkers and molecular subtypes in human membranous nephropathy |
| title_full | Integrated bioinformatics analysis for identifying fibroblast-associated biomarkers and molecular subtypes in human membranous nephropathy |
| title_fullStr | Integrated bioinformatics analysis for identifying fibroblast-associated biomarkers and molecular subtypes in human membranous nephropathy |
| title_full_unstemmed | Integrated bioinformatics analysis for identifying fibroblast-associated biomarkers and molecular subtypes in human membranous nephropathy |
| title_short | Integrated bioinformatics analysis for identifying fibroblast-associated biomarkers and molecular subtypes in human membranous nephropathy |
| title_sort | integrated bioinformatics analysis for identifying fibroblast associated biomarkers and molecular subtypes in human membranous nephropathy |
| topic | Membranous nephropathy Fibroblasts Biomarkers Molecular subtypes Integrated bioinformatics |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024144556 |
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