Discriminant analysis followed by unsupervised cluster analysis including exosomal cystatins predict presence of chronic rhinosinusitis, phenotype, and disease severity
© 2019 ARS-AAOA, LLC..
BACKGROUND: Cystatins are epithelial protease inhibitors that participate in sinonasal immunity and inflammation. Nasal mucus-derived exosomes (NMDEs) are small vesicles secreted by epithelial cells that carry protein cargo reflective of their host cell. NMDEs have been used as a noninvasive biomarker source to study chronic rhinosinusitis with nasal polyps (CRSwNP) proteomics with superior sensitivity to whole mucus. The purpose of this study was to noninvasively quantify exosomal cystatins in a heterogenous population to determine their utility in predicting phenotype and disease severity.
METHODS: This was an Institutional Review Board-approved study in which NMDEs were purified from 105 patients undergoing sinonasal surgery by ultracentrifugation. Demographic and clinical variables were collected and phenotypes were assigned a priori. Linear discriminant analysis was executed based on normalized Cystatin values as phenotype predictor variables. Unsupervised cluster analysis was performed using Ward's linkage followed by Duda/Hart Je(2)/Je(1) index cluster stopping rules. Analysis of variance (ANOVA), Welch's test, and Fisher's exact tests were used for continuous and categorical variables.
RESULTS: NMDE Cystatin-2 expression segregated by phenotype (mean ± standard error [SEM]): control (23.4 ± 4.2 pg/µg, n = 32); CRS without NP (CRSsNP) (56.6 ± 8.3 pg/µg, n = 33); and CRSwNP (130.5 ± 16.7 pg/µg, n = 40) (p < 0.0001). Seven clusters were identified among patients where the highest NMDE Cystatin-2 levels clustered with asthma, tissue eosinophilia, and aspirin-exacerbated respiratory disease (AERD).
CONCLUSION: Cystatin levels in NMDEs predict CRS phenotype and disease severity. As a "liquid biopsy," noninvasive NMDE collection offers a promising opportunity to study disease pathophysiology, discriminate disease states, and potentially reveal novel therapeutic targets.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
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| Enthalten in: |
International forum of allergy & rhinology - 9(2019), 9 vom: 04. Sept., Seite 1069-1076 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Miyake, Michelle M [VerfasserIn] |
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| Links: |
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| Themen: |
CST2 protein, human |
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| Anmerkungen: |
Date Completed 27.05.2020 Date Revised 27.05.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/alr.22380 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM299353060 |
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| 100 | 1 | |a Miyake, Michelle M |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Discriminant analysis followed by unsupervised cluster analysis including exosomal cystatins predict presence of chronic rhinosinusitis, phenotype, and disease severity |
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| 500 | |a Date Revised 27.05.2020 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2019 ARS-AAOA, LLC. | ||
| 520 | |a BACKGROUND: Cystatins are epithelial protease inhibitors that participate in sinonasal immunity and inflammation. Nasal mucus-derived exosomes (NMDEs) are small vesicles secreted by epithelial cells that carry protein cargo reflective of their host cell. NMDEs have been used as a noninvasive biomarker source to study chronic rhinosinusitis with nasal polyps (CRSwNP) proteomics with superior sensitivity to whole mucus. The purpose of this study was to noninvasively quantify exosomal cystatins in a heterogenous population to determine their utility in predicting phenotype and disease severity | ||
| 520 | |a METHODS: This was an Institutional Review Board-approved study in which NMDEs were purified from 105 patients undergoing sinonasal surgery by ultracentrifugation. Demographic and clinical variables were collected and phenotypes were assigned a priori. Linear discriminant analysis was executed based on normalized Cystatin values as phenotype predictor variables. Unsupervised cluster analysis was performed using Ward's linkage followed by Duda/Hart Je(2)/Je(1) index cluster stopping rules. Analysis of variance (ANOVA), Welch's test, and Fisher's exact tests were used for continuous and categorical variables | ||
| 520 | |a RESULTS: NMDE Cystatin-2 expression segregated by phenotype (mean ± standard error [SEM]): control (23.4 ± 4.2 pg/µg, n = 32); CRS without NP (CRSsNP) (56.6 ± 8.3 pg/µg, n = 33); and CRSwNP (130.5 ± 16.7 pg/µg, n = 40) (p < 0.0001). Seven clusters were identified among patients where the highest NMDE Cystatin-2 levels clustered with asthma, tissue eosinophilia, and aspirin-exacerbated respiratory disease (AERD) | ||
| 520 | |a CONCLUSION: Cystatin levels in NMDEs predict CRS phenotype and disease severity. As a "liquid biopsy," noninvasive NMDE collection offers a promising opportunity to study disease pathophysiology, discriminate disease states, and potentially reveal novel therapeutic targets | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a chronic rhinosinusitis | |
| 650 | 4 | |a cluster analysis | |
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| 650 | 4 | |a sinonasal mucus | |
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| 650 | 7 | |a Salivary Cystatins |2 NLM | |
| 700 | 1 | |a Workman, Alan D |e verfasserin |4 aut | |
| 700 | 1 | |a Nocera, Angela L |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Dawei |e verfasserin |4 aut | |
| 700 | 1 | |a Mueller, Sarina K |e verfasserin |4 aut | |
| 700 | 1 | |a Finn, Kristen |e verfasserin |4 aut | |
| 700 | 1 | |a Amiji, Mansoor M |e verfasserin |4 aut | |
| 700 | 1 | |a Bleier, Benjamin S |e verfasserin |4 aut | |
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