Distinct gene expression profiles and regulation networks of nasal polyps in eosinophilic and non‐eosinophilic chronic rhinosinusitis

Okada, Naoko; Nakayama, Tsuguhisa; Asaka, Daiya; Inoue, N.; Tsurumoto, Tadao; Takaishi, Shinya; Otori, Nobuyoshi; Kojima, Hiromi; Matsuda, Akio; Oboki, Keisuke; Saito, Hirohisa; Matsumoto, Kenji; Yoshikawa, Mamoru

doi:10.1002/alr.22083

Cited by 45 publications

(45 citation statements)

References 32 publications

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“…In CRS with nasal polyps (CRSwNP), polyp tissue gene expression analyzed by hierarchical clustering and principal component analysis showed the presence of a complex endotype for both eosinophilic and non-eosinophilic phenotypes. Type 2 cytokines (IL-4, IL-5, CSF2) and cell cycle regulators (cyclindependent kinase inhibitor 1A and cyclin D1) were identified in association with tissue eosinophilia, while mainly interferons and acute inflammatory cytokines (IL-1 and IL-6) were demonstrated as upstream regulators in the non-eosinophilic phenotype (34).…”

Section: Complex Molecular Pathobiology Defines New Endotypes and Submentioning

confidence: 99%

Precision medicine and phenotypes, endotypes, genotypes, regiotypes, and theratypes of allergic diseases

Agache

Akdiş

2019

Journal of Clinical Investigation

209

166

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in which microRNAs (miRNAs) play a central role (Table 3). High-throughput profiling studies of well-characterized patients, including analyses of gene expression (e.g., microarrays and RNA sequencing transcriptomics), can help to identify combined signatures for type 2 and non-type 2 endotypes. They are enriching the available data for the identification of new potential targets. As critical components in the regulation of tissue homeostasis, miRNAs represent a very attractive field of precision medicine research in asthma and allergic diseases, as they have been linked to many biological mechanisms underlying Th2 cell and macrophage polarization, regulation of ILC2 biology, steroidresistant asthma phenotype, airway smooth muscle dysfunction, and impaired antiviral innate immunity (Table 3 and refs. 15-25). Thus, miRNAs represent a modifiable downstream target that will expand the precision medicine approach beyond the type 2/ non-type 2 paradigm. In one notable example of this approach, the use of gene expression microarrays on bronchial epithelial cells obtained from patients with asthma led to the identification of periostin, an IL-13-responsive biomarker (26-30). However, expression signatures are not highly specific for type 2 asthma: a recent study showed type 2 airway gene expression in a subset of patients with chronic obstructive pulmonary disease (COPD) (31).

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Section: Complex Molecular Pathobiology Defines New Endotypes and Submentioning

confidence: 99%

Precision medicine and phenotypes, endotypes, genotypes, regiotypes, and theratypes of allergic diseases

Agache

Akdiş

2019

Journal of Clinical Investigation

209

166

View full text Add to dashboard Cite

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“…IL‐4 and IL‐13 are thought to induce local immunoglobulin E (IgE) production and increase production of mucus, whereas IL‐5 acts through activation and recruitment of eosinophils . Other Th2‐related gene transcripts, including those of CLC, CCL23, and CCL26, have also been shown to be elevated in eosinophilic CRSwNP . For these reasons, cytokine profiles are heavily investigated as diagnostic and therapeutic targets in CRSwNP.…”

Section: Summary Of Known Mrna and Protein Alterations In Eosinophilimentioning

confidence: 99%

Translating transcription: proteomics in chronic rhinosinusitis with nasal polyps reveals significant discordance with messenger RNA expression

Workman

Nocera

Müller

et al. 2019

Int Forum Allergy Rhinol

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Background: Much of the literature examining chronic rhinosinusitis with nasal polyps (CRSwNP) immunopathology has been predicated on messenger RNA (mRNA) analysis with the assumption that transcriptional changes would reflect end-effector protein expression. The purpose of this study was to test this hypothesis using matched transcriptomic and proteomic data sets. Methods:Matched tissue proteomic and transcriptomic arrays were quantified in CRSwNP polyp tissue and control inferior turbinate tissue (n = 10/group). Mucus samples were additionally collected in 6 subjects from each group. Proteins were grouped into functional categories by bioinformatics and differential expression analyses. Log-log regression and Pearson correlations were performed to determine the level of agreement between data sets. Results:Of the 1310 proteins examined, 393 were significantly differentially expressed in CRSwNP. On regression analysis, differences in protein expression were poorly predicted by differences in mRNA expression (R 2 = 0.020, p < 0.05). Several genes canonically thought to be overexpressed in CRSwNP, including IL-5, IL-13, TSLP, CCL13, and CCL26, showed substantial increases in mRNA transcription, but had minimally or unchanged protein expres-sion. Others, including IgE, periostin, CCL18, and CST1/2, were increased at both the transcriptomic and proteomic levels. Among differentially regulated proteins, tissue and mucus protein levels showed weak correlation (r = 0.26, p < 0.0001).Conclusion: Proteomic analysis in CRSwNP has revealed novel disease-associated proteins and pathways, yet correlates poorly with transcriptomic data. The increasing availability of proteomic arrays opens the door to new potential explanatory mechanisms in CRSwNP and suggests that mRNA based studies should be validated with protein analysis. C 2019 ARS-AAOA, LLC.

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“…[3][4][5][6][7][8][9][10][11][12][13] Distinctions in underlying inflammatory processes have been identified based on different patient populations (in particular, European and North American compared with Asian patients), associated cystic fibrosis, and markers of eosinophilia. 8,9,[14][15][16][17][18][19] Mixed inflammatory types (T helper (Th)-1, Th-2, and/or Th-17-type markers elevated in parallel) have also been observed in some patients. 6,13 Inadequate delineation of subtypes of CRS is likely to have hindered previous efforts to identify specific disease mechanisms, and to make informed treatment decisions.…”

mentioning

confidence: 99%

Assessing tissue transcription biomarkers of chronic rhinosinusitis: a comparison of sampling methodologies

Hoggard

Douglas

Taylor

et al. 2020

Int Forum Allergy Rhinol

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Background Chronic rhinosinusitis (CRS) is a spectrum of complex inflammatory conditions of the sinonasal mucosa. Identification of biomarkers that enable classification and improved delineation among CRS endotypes is of increasing interest. However, the extent to which less invasive sampling methods identify genuine tissue inflammatory patterns is not well understood. The aim of this study was to investigate mucosal swab and cytobrush sampling as less invasive proxies for tissue transcription levels of putative biomarkers of CRS. Methods Expression levels of 21 biomarkers of interest were assessed via custom TaqMan array cards from mucosal biopsy, cytobrush, and swab samples, in 32 patients with CRS. Reported expression levels were compared between each of the 3 sample types within each patient. Results Reported transcription levels from swab samples for IL33, MUC5AC, IL1RN, CXCL8 (IL‐8), TNF, IFNG, IL5, OSM, IL1A, and IL17C, and cytobrush levels for IL33, MUC5AC, IL5RA, IL1RN, CXCL8 (IL‐8), and IL5 were significantly different to tissue levels from matched biopsy samples. Conclusion Reported expression via swab and cytobrush sampling differed from patterns observed in matched tissue for 10 of 21 and 6 of 21 markers, respectively. Non–biopsy‐based studies for these particular markers may therefore not adequately represent tissue inflammatory processes and should be interpreted with caution. Cytobrush samples largely tracked tissue patterns for the remaining target biomarkers. In these cases, cytobrush sampling appears to adequately reflect tissue patterns for several putative biomarkers of CRS, supporting their use in clinical and research settings as a less‐invasive proxy for the assessment of mucosal tissue inflammatory transcription patterns.

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Distinct gene expression profiles and regulation networks of nasal polyps in eosinophilic and non‐eosinophilic chronic rhinosinusitis

Abstract: These results are useful for understanding the molecular basis of the mechanisms of CRSwNP and point to new targets for developing specific biomarkers and personalized therapeutic strategies for CRSwNP.

Cited by 45 publications

References 32 publications

Precision medicine and phenotypes, endotypes, genotypes, regiotypes, and theratypes of allergic diseases

Precision medicine and phenotypes, endotypes, genotypes, regiotypes, and theratypes of allergic diseases

Translating transcription: proteomics in chronic rhinosinusitis with nasal polyps reveals significant discordance with messenger RNA expression

Assessing tissue transcription biomarkers of chronic rhinosinusitis: a comparison of sampling methodologies

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