Inflammatory molecular endotypes of nasal polyps derived from White and Japanese populations

Nakayama, Tsuguhisa; Lee, Ivan T.; Le, Wei; Tsunemi, Yuichiro; Borchard, Nicole A.; Zarabanda, David; Dholakia, Sachi S.; Gall, Philip A.; Yang, Angela; Kim, Dayoung; Akutsu, Makoto; Kashiwagi, Takashi; Patel, Zara M.; Hwang, Peter H.; Frank, Daniel N.; Haruna, Shinichi; Ramakrishnan, Vijay R.; Nolan, Garry P.; Jiang, Sizun; Nayak, Jayakar V.

doi:10.1016/j.jaci.2021.11.017

Cited by 41 publications

(23 citation statements)

References 66 publications

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“…In addition, CCL11 (eotaxin) was upregulated in ECRS and nonECRS, and CCL24 (eotaxin-2) was not identified in any CRSwNPs. Previous reports mentioned that type 2 inflammatory transcript expression of CCL13 , CCL18 , and CCL26 were upregulated in the type 2 endotype [ 7 ] and ECRS compared with nonECRS [ 8 ]. It is known that CCL11 , CCL13 , and CCL26 recruit eosinophils, basophils, mast cells, and CD4 (+) T helper 2 cells [ 14 ], and CCL18 recruits naive T cells, B cells, immature dendritic cells, and activate fibroblasts [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

“…Currently, JESREC criteria are used to classify ECRS into mild, moderate, and severe ECRS [ 4 ]. From a transcriptome analysis of nasal polyps, it was certified that nasal polyps can be segregated into two major endotypes showing a type 2 or non-type 2 endotype [ 7 ]. However, a previous study using a transcriptome analysis with three ECRS, three nonECRS, and three control subjects showed no distinct differentiation of expressed mRNAs between ECRS and nonECRS [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

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Distinct Gene Set Enrichment Profiles in Eosinophilic and Non-Eosinophilic Chronic Rhinosinusitis with Nasal Polyps by Bulk RNA Barcoding and Sequencing

Ishino

Takeno

Takemoto

et al. 2022

IJMS

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Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease with a high symptom burden, including nasal congestion and smell disorders. This study performed a detailed transcriptomic analysis in CRSwNP classified as eosinophilic CRS (ECRS), nonECRS according to the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) criteria, and a group of ECRS with comorbid aspirin intolerant asthma (Asp). Gene expression profiles of nasal polyps and the uncinate process in CRSwNP patients and normal subjects (controls) were generated by bulk RNA barcoding and sequencing (BRB-seq). A differentially expressed genes (DEGs) analysis was performed using DESeq2 software in iDEP to clarify any relationship between gene expression and disease backgrounds. A total of 3004 genes were identified by DEGs analysis to be associated with ECRS vs control, nonECRS vs control, and Asp vs control. A pathway analysis showed distinct profiles between the groups. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) showed distinct phenotype-specific pathways of expressed genes. In the specific pathway of “cytokine–cytokine receptor interaction”, the differentially expressed genes were widely distributed. This study indicates that transcriptome analysis using BRB-seq may be a valuable tool to explore the pathogenesis of type 2 inflammation in CRSwNP.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Distinct Gene Set Enrichment Profiles in Eosinophilic and Non-Eosinophilic Chronic Rhinosinusitis with Nasal Polyps by Bulk RNA Barcoding and Sequencing

Ishino

Takeno

Takemoto

et al. 2022

IJMS

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“…Figure 1 shows the workflow chart of this study. The Bioconductor package “GEOquery” 34 of R software (version 4.1.0, http://r-project.org/ ) was used to extract the CRSwNP expression profile datasets GSE136825 35 , GSE36830 36 , GSE179265 37 and GSE169376 38 from the Gene Expression Omnibus (GEO) database ( https://www.ncbi.nlm.nih.gov/geo/ ). The mRNA and lncRNA data from GSE136825 and the miRNA data from GSE169376 were sorted into standardized original data for subsequent analysis.…”

Section: Methodsmentioning

confidence: 99%

Construction and analysis of a ceRNA network and patterns of immune infiltration in chronic rhinosinusitis with nasal polyps: based on data mining and experimental verification

Chen

Xing

Yang

et al. 2022

Sci Rep

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Recent studies have revealed the significant role of the competing endogenous RNA (ceRNA) network in human diseases. However, systematic analysis of the ceRNA mechanism in chronic rhinosinusitis with nasal polyps (CRSwNP) is limited. In this study, we constructed a competitive endogenous RNA (ceRNA) network and identified a potential regulatory axis in CRSwNP based on bioinformatics analysis and experimental verification. We obtained lncRNA, miRNA, and mRNA expression profiles from the Gene Expression Omnibus. After analysis of CRSwNP patients and the control groups, we identified 565 DE-lncRNAs, 23 DE-miRNAs, and 1799 DE-mRNAs by the DESeq2 R package or limma R package. Enrichment analysis of 1799 DE-mRNAs showed that CRSwNP was associated with inflammation and immunity. Moreover, we identified 21 lncRNAs, 8 miRNAs and 8 mRNAs to construct the lncRNA-miRNA-mRNA ceRNA network. A potential MIAT/miR-125a/IRF4 axis was determined according to the degree and positive correlation between a lncRNA and its competitive endogenous mRNAs. The GSEA results suggested that IRF4 may be involved in immune cell infiltration. The validation of another dataset confirmed that MIAT and IRF4 were differentially expressed between the CRSwNP and control groups. The area under the ROC curve (AUC) of MIAT and IRF4 was 0.944. The CIBERSORT analysis revealed that eosinophils and M2 macrophages may be involved in the CRSwNP process. MIAT was correlated with dendritic cells and M2 macrophages, and IRF4 was correlated with dendritic cells. Finally, to validate the key genes, we performed in-silico validation using another dataset and experimental validation using immunohistochemistry, immunofluorescence, and Western blot. In summary, the constructed novel MIAT/miR-125a/IRF4 axis may play a critical role in the development and progression of CRSwNP. We believe that the ceRNA network and immune cell infiltration could offer further insight into novel molecular therapeutic targets for CRSwNP.

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“…GSE136825 ( 14 ) and GSE179265 ( 15 ) datasets were downloaded from Gene Expression Omnibus (GEO) database ( ). GSE136825 dataset was consisted of 28 inferior turbinate tissues from healthy control subjects and 42 nasal polyp tissues from CRSwNP patients while GSE179265 dataset included seven normal uncinate process tissues and 17 nasal polyp samples from CRSwNP patients.…”

Section: Methodsmentioning

confidence: 99%

M2 macrophage-related gene signature in chronic rhinosinusitis with nasal polyps

et al. 2022

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BackgroundChronic rhinosinusitis with nasal polyps (CRSwNP) is a common sinonasal inflammatory disorder with high heterogeneity. Increasing evidence have indicated that the infiltration of macrophages especially M2 macrophages play pivotal roles in the pathogenesis of CRSwNP, but the underlying mechanisms remain undetermined. This study sought to identify potential biomarkers related to M2 macrophages in CRSwNP.MethodsThe expression datasets of GSE136825 and GSE179265 were download from Gene Expression Omnibus (GEO) database and merged. Then, CIBERSORT and weighted gene co-expression network analysis (WGCNA) algorithms were applied to identify M2 macrophage-related gene modules. Thereafter, differentially expressed genes (DEGs) related to M2 macrophages were selected to perform functional enrichment analyses. A protein-protein interaction (PPI) network was built to identify hub genes and quantitative real-time reverse transcriptions PCR was used to verify the bioinformatics results.ResultsA total of 92 DEGs associated with M2 macrophages were identified for further analysis. The results of Gene ontology (GO) and Kyoto Encyclopedia of genes and genomes (KEGG) analyses illustrated that M2 macrophage-associated DEGs primarily enriched in immune responses and extracellular matrix structure. PPI network analysis identified 18 hub genes related to M2 macrophages that might be pivotal in the pathogenesis of CRSwNP. After verification, AIF1, C1QA, C1QB, C3AR1, CCR1, CD163, CD4, CD53, CD86, CSF1R, CYBB, FCER1G, FCGR3A, IL10RA, ITGB2, LAPTM5, PLEK, TYROBP were identified as potential M2 macrophage-related biomarkers for CRSwNP.ConclusionThese findings yield new insights into the hub genes and mechanisms related to M2 macrophages in the pathogenesis of CRSwNP. Further studies of these hub genes would help better understand the disease progression and identify potential treatment targets.

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Inflammatory molecular endotypes of nasal polyps derived from White and Japanese populations

Cited by 41 publications

References 66 publications

Distinct Gene Set Enrichment Profiles in Eosinophilic and Non-Eosinophilic Chronic Rhinosinusitis with Nasal Polyps by Bulk RNA Barcoding and Sequencing

Distinct Gene Set Enrichment Profiles in Eosinophilic and Non-Eosinophilic Chronic Rhinosinusitis with Nasal Polyps by Bulk RNA Barcoding and Sequencing

Construction and analysis of a ceRNA network and patterns of immune infiltration in chronic rhinosinusitis with nasal polyps: based on data mining and experimental verification

M2 macrophage-related gene signature in chronic rhinosinusitis with nasal polyps

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