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Published on: October 11, 2018
Integrated bioinformatics analysis for identifying fibroblast-associated biomarkers and molecular subtypes in human
Chuying Gui1, Sidi Liu1, Zhike Fu1
1The Department of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.
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.
Insights
This study identifies fibroblast-associated molecular subtypes in membranous nephropathy (MN) using bioinformatics. COL3A1 is highlighted as a key biomarker for potential diagnosis and therapy in MN patients.
Area of Science:
- Nephrology
- Immunology
- Bioinformatics
- Genomics
Background:
- Membranous nephropathy (MN) involves immune complex deposition in the glomerular basement membrane, causing proteinuria and kidney dysfunction.
- Fibroblasts play a role in MN pathogenesis through tissue remodeling and immune modulation.
Purpose of the Study:
- To identify fibroblast-associated biomarkers and molecular subtypes in membranous nephropathy (MN).
- To investigate the role of fibroblasts in MN pathogenesis using integrated bioinformatics analyses.
Main Methods:
- Utilized xCell algorithm for fibroblast infiltration assessment.
- Employed weighted gene co-expression network analysis (WGCNA) to identify fibroblast-related gene modules.
- Performed differential gene expression analysis and protein-protein interaction network construction to screen for differentially expressed fibroblast-associated genes (DEFAGs).
- Applied consensus clustering to categorize MN patients into molecular subtypes based on DEFAG expression.
Main Results:
- Fibroblast scores were significantly elevated in MN patients compared to healthy controls (HC).
- WGCNA identified key gene modules (brown and turquoise) strongly correlated with fibroblast scores.
- Identified 308 overlapping DEFAGs between WGCNA and differential expression analysis.
- Discovered two distinct molecular subtypes (C1 and C2) in MN, enriched for immune response and extracellular matrix remodeling pathways.
- Highlighted COL3A1 and TGFB1 as central biomarkers with elevated expression in MN.
Conclusions:
- Integrated bioinformatics analysis revealed fibroblast-associated molecular subtypes in MN with distinct immune profiles.
- COL3A1 is identified as a potential diagnostic and therapeutic target for membranous nephropathy.
- Findings implicate COL3A1 in immune regulation and disease progression in MN.
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