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pmid:38476235

Identification and validation of CCR5 linking keloid with atopic dermatitis through comprehensive bioinformatics analysis and machine learning.

Bin Zhou · Nuoya Zhou · Yan Liu · Enzhu Dong · Lianqi Peng · Yifei Wang · Liu Yang · Huinan Suo · Juan Tao

Frontiers in immunology · 2024 doi:10.3389/fimmu.2024.1309992

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complete

Experiment

complete

Data

partial

Analysis

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Execution

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:38476235
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title
Identification and validation of CCR5 linking keloid with atopic dermatitis through comprehensive bioinformatics analysis and machine learning.
doi
10.3389/fimmu.2024.1309992
pmid
38476235
authors array · 9 items
[0]
Bin Zhou
[1]
Nuoya Zhou
[2]
Yan Liu
[3]
Enzhu Dong
[4]
Lianqi Peng
[5]
Yifei Wang
[6]
Liu Yang
[7]
Huinan Suo
[8]
Juan Tao
journal
Frontiers in immunology
year
2024
abstract
There is sufficient evidence indicating that keloid is strongly associated with atopic dermatitis (AD) across ethnic groups. However, the molecular mechanism underlying the association is not fully understood. The aim of this study is to discover the underlying mechanism of the association between keloid and AD by integrating comprehensive bioinformatics techniques and machine learning methods. The gene expression profiles of keloid and AD were downloaded from the Gene Expression Omnibus (GEO) database. A total of 449 differentially expressed genes (DEGs) were found to be shared in keloid and AD using the training datasets of GEO (GSE158395 and GSE121212). The hub genes were identified using the protein-protein interaction network and Cytoscape software. 20 of the most significant hub genes were selected, which were mainly involved in the regulation of the inflammatory and immune response. Through two machine learning algorithms of LASSO and SVM-RFE, CCR5 was identified as the most important key gene. Subsequently, upregulated CCR5 gene expression was confirmed in validation GEO datasets (GSE188952 and GSE32924) and clinical samples of keloid and AD. Immune infiltration analysis showed that T helper (Th) 1, 2 and 17 cells were significantly enriched in the microenvironment of both keloid and AD. Positive correlations were found between CCR5 and Th1, Th2 and Th17 cells. Finally, two TFs of CCR5, NR3C2 and YY1, were identified, both of which were downregulated in keloid and AD tissues. Our study firstly reveals that keloid and AD shared common inflammatory and immune pathways. Moreover, CCR5 plays a key role in the pathogenesis association between keloid and AD. The common pathways and key genes may shed light on further mechanism research and targeted therapy, and may provide therapeutic interventions of keloid with AD.
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We used two machine learning algorithms, i.e. LASSO regression analysis and SVM-RFE algorithms to select key genes.
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We used two machine learning algorithms, i.e. LASSO regression analysis and SVM-RFE algorithms to select key genes.
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The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding authors.
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A total of 449 differentially expressed genes were shared by keloid and atopic dermatitis in the training datasets.
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sections[19] "Functional annotation of common DEGs between keloid and AD" paragraph 2
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A total of 449 DEGs were found to be shared, with 224 downregulated and 225 upregulated ( Figures 3A, B ).
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A total of 449 differentially expressed genes were shared by keloid and atopic dermatitis in the training datasets.
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n and log2 conversion were performed for the RNA-seq data. The research flowchart of this study i
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was prepared for quantitative real-time PCR (qPCR), and the △△CT method was used for data proc
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ining proteinase and phosphatase inhibitors. Western blot (WB) was performed as previously described (
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Complete file
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However, the molecular mechanism underlying the association is not fully understood. The aim of this study is to discover the underlying mechanism of the association between keloid and AD by integrating comprehensive bioinformatics techniques and machine learning methods. The gene expression profiles of keloid and AD were downloaded from the Gene Expression Omnibus (GEO) database. A total of 449 differentially expressed genes (DEGs) were found to be shared in keloid and AD using the training datasets of GEO (GSE158395 and GSE121212). The hub genes were identified using the protein-protein interaction network and Cytoscape software. 20 of the most significant hub genes were selected, which were mainly involved in the regulation of the inflammatory and immune response. Through two machine learning algorithms of LASSO and SVM-RFE, CCR5 was identified as the most important key gene. 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