Identification of hub genes and immune cell infiltration characteristics in chronic rhinosinusitis with nasal polyps: Bioinformatics analysis and experimental validation

The aim of our study is to reveal the hub genes related to the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) and their association with immune cell infiltration through bioinformatics analysis combined with experimental validation. In this study, through differential gene express...

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Main Authors: Yangwang Pan, Linjing Wu, Shuai He, Jun Wu, Tong Wang, Hongrui Zang
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-08-01
Series:Frontiers in Molecular Biosciences
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmolb.2022.843580/full
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author Yangwang Pan
Yangwang Pan
Linjing Wu
Shuai He
Jun Wu
Tong Wang
Hongrui Zang
author_facet Yangwang Pan
Yangwang Pan
Linjing Wu
Shuai He
Jun Wu
Tong Wang
Hongrui Zang
author_sort Yangwang Pan
collection DOAJ
description The aim of our study is to reveal the hub genes related to the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) and their association with immune cell infiltration through bioinformatics analysis combined with experimental validation. In this study, through differential gene expression analysis, 1,516 upregulated and 1,307 downregulated DEG were obtained from dataset GSE136825 of the GEO database. We identified 14 co-expressed modules using weighted gene co-expression network analysis (WGCNA), among which the most significant positive and negative correlations were MEgreen and MEturquoise modules, containing 1,540 and 3,710 genes respectively. After the intersection of the two modules and DEG, two gene sets—DEG-MEgreen and DEG-MEturquoise—were obtained, containing 395 and 1,168 genes respectively. Through GO term analysis, it was found that immune response and signal transduction are the most important biological processes. We found, based on KEGG pathway enrichment analysis, that osteoclast differentiations, cytokine–cytokine receptor interactions, and neuroactive ligand–receptor interactions are the most important in the two gene sets. Through PPI network analysis, we listed the top-ten genes for the concentrated connectivity of the two gene sets. Next, a few genes were verified by qPCR experiments, and FPR2, ITGAM, C3AR1, FCER1G, CYBB in DEG-MEgreen and GNG4, NMUR2, and GNG7 in DEG-MEturquoise were confirmed to be related to the pathogenesis of CRSwNP. NP immune cell infiltration analysis revealed a significant difference in the proportion of immune cells between the NP group and control group. Finally, correlation analysis between target hub genes and immune cells indicated that FPR2 and GNG7 had a positive or negative correlation with some specific immune cells. In summary, the discoveries of these new hub genes and their association with immune cell infiltration are of great significance for uncovering the specific pathogenesis of CRSwNP and searching for disease biomarkers and potential therapeutic targets.
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spelling doaj.art-c6c49eaced974688a37f2e86a3bdd4ae2022-12-22T04:02:32ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2022-08-01910.3389/fmolb.2022.843580843580Identification of hub genes and immune cell infiltration characteristics in chronic rhinosinusitis with nasal polyps: Bioinformatics analysis and experimental validationYangwang Pan0Yangwang Pan1Linjing Wu2Shuai He3Jun Wu4Tong Wang5Hongrui Zang6Department of Otolaryngology Head and Neck Surgery, Civil Aviation General Hospital (Peking University Civil Aviation School of Clinical Medicine), Bejing, ChinaDepartment of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, ChinaDepartment of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, ChinaDepartment of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, ChinaDepartment of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, ChinaDepartment of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, ChinaDepartment of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, ChinaThe aim of our study is to reveal the hub genes related to the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) and their association with immune cell infiltration through bioinformatics analysis combined with experimental validation. In this study, through differential gene expression analysis, 1,516 upregulated and 1,307 downregulated DEG were obtained from dataset GSE136825 of the GEO database. We identified 14 co-expressed modules using weighted gene co-expression network analysis (WGCNA), among which the most significant positive and negative correlations were MEgreen and MEturquoise modules, containing 1,540 and 3,710 genes respectively. After the intersection of the two modules and DEG, two gene sets—DEG-MEgreen and DEG-MEturquoise—were obtained, containing 395 and 1,168 genes respectively. Through GO term analysis, it was found that immune response and signal transduction are the most important biological processes. We found, based on KEGG pathway enrichment analysis, that osteoclast differentiations, cytokine–cytokine receptor interactions, and neuroactive ligand–receptor interactions are the most important in the two gene sets. Through PPI network analysis, we listed the top-ten genes for the concentrated connectivity of the two gene sets. Next, a few genes were verified by qPCR experiments, and FPR2, ITGAM, C3AR1, FCER1G, CYBB in DEG-MEgreen and GNG4, NMUR2, and GNG7 in DEG-MEturquoise were confirmed to be related to the pathogenesis of CRSwNP. NP immune cell infiltration analysis revealed a significant difference in the proportion of immune cells between the NP group and control group. Finally, correlation analysis between target hub genes and immune cells indicated that FPR2 and GNG7 had a positive or negative correlation with some specific immune cells. In summary, the discoveries of these new hub genes and their association with immune cell infiltration are of great significance for uncovering the specific pathogenesis of CRSwNP and searching for disease biomarkers and potential therapeutic targets.https://www.frontiersin.org/articles/10.3389/fmolb.2022.843580/fullnasal polypshub genesimmune cell infiltrationbioinformatics analysisexperimental validation
spellingShingle Yangwang Pan
Yangwang Pan
Linjing Wu
Shuai He
Jun Wu
Tong Wang
Hongrui Zang
Identification of hub genes and immune cell infiltration characteristics in chronic rhinosinusitis with nasal polyps: Bioinformatics analysis and experimental validation
Frontiers in Molecular Biosciences
nasal polyps
hub genes
immune cell infiltration
bioinformatics analysis
experimental validation
title Identification of hub genes and immune cell infiltration characteristics in chronic rhinosinusitis with nasal polyps: Bioinformatics analysis and experimental validation
title_full Identification of hub genes and immune cell infiltration characteristics in chronic rhinosinusitis with nasal polyps: Bioinformatics analysis and experimental validation
title_fullStr Identification of hub genes and immune cell infiltration characteristics in chronic rhinosinusitis with nasal polyps: Bioinformatics analysis and experimental validation
title_full_unstemmed Identification of hub genes and immune cell infiltration characteristics in chronic rhinosinusitis with nasal polyps: Bioinformatics analysis and experimental validation
title_short Identification of hub genes and immune cell infiltration characteristics in chronic rhinosinusitis with nasal polyps: Bioinformatics analysis and experimental validation
title_sort identification of hub genes and immune cell infiltration characteristics in chronic rhinosinusitis with nasal polyps bioinformatics analysis and experimental validation
topic nasal polyps
hub genes
immune cell infiltration
bioinformatics analysis
experimental validation
url https://www.frontiersin.org/articles/10.3389/fmolb.2022.843580/full
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