Identification of key biomarkers of the glomerulus in focal segmental glomerulosclerosis and their relationship with immune cell infiltration based on WGCNA and the LASSO algorithm

AbstractObjective The aim of our study was to identify key biomarkers of glomeruli in focal glomerulosclerosis (FSGS) and analyze their relationship with the infiltration of immune cells.Methods The expression profiles (GSE108109 and GSE200828) were obtained from the GEO database. The differentially...

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Main Authors: Yun Xia Zhang, Juan Lv, Jun Yuan Bai, XiaoWei Pu, En Lai Dai
Format: Article
Language:English
Published: Taylor & Francis Group 2023-12-01
Series:Renal Failure
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/0886022X.2023.2202264
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author Yun Xia Zhang
Juan Lv
Jun Yuan Bai
XiaoWei Pu
En Lai Dai
author_facet Yun Xia Zhang
Juan Lv
Jun Yuan Bai
XiaoWei Pu
En Lai Dai
author_sort Yun Xia Zhang
collection DOAJ
description AbstractObjective The aim of our study was to identify key biomarkers of glomeruli in focal glomerulosclerosis (FSGS) and analyze their relationship with the infiltration of immune cells.Methods The expression profiles (GSE108109 and GSE200828) were obtained from the GEO database. The differentially expressed genes (DEGs) were filtered and analyzed by gene set enrichment analysis (GSEA). MCODE module was constructed. Weighted gene coexpression network analysis (WGCNA) was performed to obtain the core gene modules. Least absolute shrinkage and selection operator (LASSO) regression was applied to identify key genes. ROC curves were employed to explore their diagnostic accuracy. Transcription factor prediction of the key biomarkers was performed using the Cytoscape plugin IRegulon. The analysis of the infiltration of 28 immune cells and their correlation with the key biomarkers were performed.Results A total of 1474 DEGs were identified. Their functions were mostly related to immune-related diseases and signaling pathways. MCODE identified five modules. The turquoise module of WGCNA had significant relevance to the glomerulus in FSGS. TGFB1 and NOTCH1 were identified as potential key glomerular biomarkers in FSGS. Eighteen transcription factors were obtained from the two hub genes. Immune infiltration showed significant correlations with T cells. The results of immune cell infiltration and their relationship with key biomarkers implied that NOTCH1 and TGFB1 were enhanced in immune-related pathways.Conclusion TGFB1 and NOTCH1 may be strongly correlated with the pathogenesis of the glomerulus in FSGS and are new candidate key biomarkers. T-cell infiltration plays an essential role in the FSGS lesion process.
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spelling doaj.art-38ba99ee81004b10b28300f8bfa7677f2023-10-17T09:23:24ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492023-12-0145110.1080/0886022X.2023.2202264Identification of key biomarkers of the glomerulus in focal segmental glomerulosclerosis and their relationship with immune cell infiltration based on WGCNA and the LASSO algorithmYun Xia Zhang0Juan Lv1Jun Yuan Bai2XiaoWei Pu3En Lai Dai4College of Integrated Traditional and Western Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou, ChinaCollege of Integrated Traditional and Western Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou, ChinaCollege of Integrated Traditional and Western Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou, ChinaCollege of Integrated Traditional and Western Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou, ChinaCollege of Integrated Traditional and Western Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou, ChinaAbstractObjective The aim of our study was to identify key biomarkers of glomeruli in focal glomerulosclerosis (FSGS) and analyze their relationship with the infiltration of immune cells.Methods The expression profiles (GSE108109 and GSE200828) were obtained from the GEO database. The differentially expressed genes (DEGs) were filtered and analyzed by gene set enrichment analysis (GSEA). MCODE module was constructed. Weighted gene coexpression network analysis (WGCNA) was performed to obtain the core gene modules. Least absolute shrinkage and selection operator (LASSO) regression was applied to identify key genes. ROC curves were employed to explore their diagnostic accuracy. Transcription factor prediction of the key biomarkers was performed using the Cytoscape plugin IRegulon. The analysis of the infiltration of 28 immune cells and their correlation with the key biomarkers were performed.Results A total of 1474 DEGs were identified. Their functions were mostly related to immune-related diseases and signaling pathways. MCODE identified five modules. The turquoise module of WGCNA had significant relevance to the glomerulus in FSGS. TGFB1 and NOTCH1 were identified as potential key glomerular biomarkers in FSGS. Eighteen transcription factors were obtained from the two hub genes. Immune infiltration showed significant correlations with T cells. The results of immune cell infiltration and their relationship with key biomarkers implied that NOTCH1 and TGFB1 were enhanced in immune-related pathways.Conclusion TGFB1 and NOTCH1 may be strongly correlated with the pathogenesis of the glomerulus in FSGS and are new candidate key biomarkers. T-cell infiltration plays an essential role in the FSGS lesion process.https://www.tandfonline.com/doi/10.1080/0886022X.2023.2202264Focal segmental glomerulosclerosisweighted gene coexpression network analysisleast absolute shrinkage and selection operatorimmune cell infiltrationTGFB1NOTCH1
spellingShingle Yun Xia Zhang
Juan Lv
Jun Yuan Bai
XiaoWei Pu
En Lai Dai
Identification of key biomarkers of the glomerulus in focal segmental glomerulosclerosis and their relationship with immune cell infiltration based on WGCNA and the LASSO algorithm
Renal Failure
Focal segmental glomerulosclerosis
weighted gene coexpression network analysis
least absolute shrinkage and selection operator
immune cell infiltration
TGFB1
NOTCH1
title Identification of key biomarkers of the glomerulus in focal segmental glomerulosclerosis and their relationship with immune cell infiltration based on WGCNA and the LASSO algorithm
title_full Identification of key biomarkers of the glomerulus in focal segmental glomerulosclerosis and their relationship with immune cell infiltration based on WGCNA and the LASSO algorithm
title_fullStr Identification of key biomarkers of the glomerulus in focal segmental glomerulosclerosis and their relationship with immune cell infiltration based on WGCNA and the LASSO algorithm
title_full_unstemmed Identification of key biomarkers of the glomerulus in focal segmental glomerulosclerosis and their relationship with immune cell infiltration based on WGCNA and the LASSO algorithm
title_short Identification of key biomarkers of the glomerulus in focal segmental glomerulosclerosis and their relationship with immune cell infiltration based on WGCNA and the LASSO algorithm
title_sort identification of key biomarkers of the glomerulus in focal segmental glomerulosclerosis and their relationship with immune cell infiltration based on wgcna and the lasso algorithm
topic Focal segmental glomerulosclerosis
weighted gene coexpression network analysis
least absolute shrinkage and selection operator
immune cell infiltration
TGFB1
NOTCH1
url https://www.tandfonline.com/doi/10.1080/0886022X.2023.2202264
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