Do sputum or circulating blood samples reflect the pulmonary transcriptomic differences of COPD patients? A multi-tissue transcriptomic network META-analysis

BACKGROUND: Previous studies have identified lung, sputum or blood transcriptomic biomarkers associated with the severity of airflow limitation in COPD. Yet, it is not clear whether the lung pathobiology is mirrored by these surrogate tissues. The aim of this study was to explore this question. METH...

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Autores: Faner, Rosa, Morrow, Jarrett D., Casas Recasens, Sandra, Cloonan, Suzanne M., Noell, Guillaume, López Giraldo, Alejandra, Tal-Singer, Ruth, Miller, Bruce E., Silverman, Edwin K., Agustí García-Navarro, Àlvar, Hersh, Craig P.
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/132914
Acesso em linha:https://hdl.handle.net/2445/132914
Access Level:acceso abierto
Palavra-chave:Malalties pulmonars obstructives cròniques
Bronquitis
Esput
Marcadors bioquímics
Chronic obstructive pulmonary diseases
Bronchitis
Sputum
Biochemical markers
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spelling Do sputum or circulating blood samples reflect the pulmonary transcriptomic differences of COPD patients? A multi-tissue transcriptomic network META-analysisFaner, RosaMorrow, Jarrett D.Casas Recasens, SandraCloonan, Suzanne M.Noell, GuillaumeLópez Giraldo, AlejandraTal-Singer, RuthMiller, Bruce E.Silverman, Edwin K.Agustí García-Navarro, ÀlvarHersh, Craig P.Malalties pulmonars obstructives cròniquesBronquitisEsputMarcadors bioquímicsChronic obstructive pulmonary diseasesBronchitisSputumBiochemical markersBACKGROUND: Previous studies have identified lung, sputum or blood transcriptomic biomarkers associated with the severity of airflow limitation in COPD. Yet, it is not clear whether the lung pathobiology is mirrored by these surrogate tissues. The aim of this study was to explore this question. METHODS: We used Weighted Gene Co-expression Network Analysis (WGCNA) to identify shared pathological mechanisms across four COPD gene-expression datasets: two sets of lung tissues (L1 n = 70; L2 n = 124), and one each of induced sputum (S; n = 121) and peripheral blood (B; n = 121). RESULTS: WGCNA analysis identified twenty-one gene co-expression modules in L1. A robust module preservation between the two L datasets was observed (86%), with less preservation in S (33%) and even less in B (23%). Three modules preserved across lung tissues and sputum (not blood) were associated with the severity of airflow limitation. Ontology enrichment analysis showed that these modules included genes related to mitochondrial function, ion-homeostasis, T cells and RNA processing. These findings were largely reproduced using the consensus WGCNA network approach. CONCLUSIONS: These observations indicate that major differences in lung tissue transcriptomics in patients with COPD are poorly mirrored in sputum and are unrelated to those determined in blood, suggesting that the systemic component in COPD is independently regulated. Finally, the fact that one of the preserved modules associated with FEV1 was enriched in mitochondria-related genes supports a role for mitochondrial dysfunction in the pathobiology of COPD.BioMed Central2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/132914Articles publicats en revistes (Medicina)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1186/s12931-018-0965-yRespiratory Research, 2019, vol. 20, num. 1, p. 5https://doi.org/10.1186/s12931-018-0965-ycc-by (c) Faner, Rosa et al., 2019http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1329142026-05-27T06:46:51Z
dc.title.none.fl_str_mv Do sputum or circulating blood samples reflect the pulmonary transcriptomic differences of COPD patients? A multi-tissue transcriptomic network META-analysis
title Do sputum or circulating blood samples reflect the pulmonary transcriptomic differences of COPD patients? A multi-tissue transcriptomic network META-analysis
spellingShingle Do sputum or circulating blood samples reflect the pulmonary transcriptomic differences of COPD patients? A multi-tissue transcriptomic network META-analysis
Faner, Rosa
Malalties pulmonars obstructives cròniques
Bronquitis
Esput
Marcadors bioquímics
Chronic obstructive pulmonary diseases
Bronchitis
Sputum
Biochemical markers
title_short Do sputum or circulating blood samples reflect the pulmonary transcriptomic differences of COPD patients? A multi-tissue transcriptomic network META-analysis
title_full Do sputum or circulating blood samples reflect the pulmonary transcriptomic differences of COPD patients? A multi-tissue transcriptomic network META-analysis
title_fullStr Do sputum or circulating blood samples reflect the pulmonary transcriptomic differences of COPD patients? A multi-tissue transcriptomic network META-analysis
title_full_unstemmed Do sputum or circulating blood samples reflect the pulmonary transcriptomic differences of COPD patients? A multi-tissue transcriptomic network META-analysis
title_sort Do sputum or circulating blood samples reflect the pulmonary transcriptomic differences of COPD patients? A multi-tissue transcriptomic network META-analysis
dc.creator.none.fl_str_mv Faner, Rosa
Morrow, Jarrett D.
Casas Recasens, Sandra
Cloonan, Suzanne M.
Noell, Guillaume
López Giraldo, Alejandra
Tal-Singer, Ruth
Miller, Bruce E.
Silverman, Edwin K.
Agustí García-Navarro, Àlvar
Hersh, Craig P.
author Faner, Rosa
author_facet Faner, Rosa
Morrow, Jarrett D.
Casas Recasens, Sandra
Cloonan, Suzanne M.
Noell, Guillaume
López Giraldo, Alejandra
Tal-Singer, Ruth
Miller, Bruce E.
Silverman, Edwin K.
Agustí García-Navarro, Àlvar
Hersh, Craig P.
author_role author
author2 Morrow, Jarrett D.
Casas Recasens, Sandra
Cloonan, Suzanne M.
Noell, Guillaume
López Giraldo, Alejandra
Tal-Singer, Ruth
Miller, Bruce E.
Silverman, Edwin K.
Agustí García-Navarro, Àlvar
Hersh, Craig P.
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Malalties pulmonars obstructives cròniques
Bronquitis
Esput
Marcadors bioquímics
Chronic obstructive pulmonary diseases
Bronchitis
Sputum
Biochemical markers
topic Malalties pulmonars obstructives cròniques
Bronquitis
Esput
Marcadors bioquímics
Chronic obstructive pulmonary diseases
Bronchitis
Sputum
Biochemical markers
description BACKGROUND: Previous studies have identified lung, sputum or blood transcriptomic biomarkers associated with the severity of airflow limitation in COPD. Yet, it is not clear whether the lung pathobiology is mirrored by these surrogate tissues. The aim of this study was to explore this question. METHODS: We used Weighted Gene Co-expression Network Analysis (WGCNA) to identify shared pathological mechanisms across four COPD gene-expression datasets: two sets of lung tissues (L1 n = 70; L2 n = 124), and one each of induced sputum (S; n = 121) and peripheral blood (B; n = 121). RESULTS: WGCNA analysis identified twenty-one gene co-expression modules in L1. A robust module preservation between the two L datasets was observed (86%), with less preservation in S (33%) and even less in B (23%). Three modules preserved across lung tissues and sputum (not blood) were associated with the severity of airflow limitation. Ontology enrichment analysis showed that these modules included genes related to mitochondrial function, ion-homeostasis, T cells and RNA processing. These findings were largely reproduced using the consensus WGCNA network approach. CONCLUSIONS: These observations indicate that major differences in lung tissue transcriptomics in patients with COPD are poorly mirrored in sputum and are unrelated to those determined in blood, suggesting that the systemic component in COPD is independently regulated. Finally, the fact that one of the preserved modules associated with FEV1 was enriched in mitochondria-related genes supports a role for mitochondrial dysfunction in the pathobiology of COPD.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/132914
url https://hdl.handle.net/2445/132914
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1186/s12931-018-0965-y
Respiratory Research, 2019, vol. 20, num. 1, p. 5
https://doi.org/10.1186/s12931-018-0965-y
dc.rights.none.fl_str_mv cc-by (c) Faner, Rosa et al., 2019
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Faner, Rosa et al., 2019
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv Articles publicats en revistes (Medicina)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301603

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