Cargando…
Effect of short-term oral prednisone therapy on blood gene expression: a randomised controlled clinical trial
BACKGROUND: Effects of systemic corticosteroids on blood gene expression are largely unknown. This study determined gene expression signature associated with short-term oral prednisone therapy in patients with chronic obstructive pulmonary disease (COPD) and its relationship to 1-year mortality foll...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683462/ https://www.ncbi.nlm.nih.gov/pubmed/31382977 http://dx.doi.org/10.1186/s12931-019-1147-2 |
_version_ | 1783442097172381696 |
---|---|
author | Takiguchi, Hiroto Chen, Virginia Obeidat, Ma’en Hollander, Zsuzsanna FitzGerald, J. Mark McManus, Bruce M. Ng, Raymond T. Sin, Don D. |
author_facet | Takiguchi, Hiroto Chen, Virginia Obeidat, Ma’en Hollander, Zsuzsanna FitzGerald, J. Mark McManus, Bruce M. Ng, Raymond T. Sin, Don D. |
author_sort | Takiguchi, Hiroto |
collection | PubMed |
description | BACKGROUND: Effects of systemic corticosteroids on blood gene expression are largely unknown. This study determined gene expression signature associated with short-term oral prednisone therapy in patients with chronic obstructive pulmonary disease (COPD) and its relationship to 1-year mortality following an acute exacerbation of COPD (AECOPD). METHODS: Gene expression in whole blood was profiled using the Affymetrix Human Gene 1.1 ST microarray chips from two cohorts: 1) a prednisone cohort with 37 stable COPD patients randomly assigned to prednisone 30 mg/d + standard therapy for 4 days or standard therapy alone and 2) the Rapid Transition Program (RTP) cohort with 218 COPD patients who experienced AECOPD and were treated with systemic corticosteroids. All gene expression data were adjusted for the total number of white blood cells and their differential cell counts. RESULTS: In the prednisone cohort, 51 genes were differentially expressed between prednisone and standard therapy group at a false discovery rate of < 0.05. The top 3 genes with the largest fold-changes were KLRF1, GZMH and ADGRG1; and 21 genes were significantly enriched in immune system pathways including the natural killer cell mediated cytotoxicity. In the RTP cohort, 27 patients (12.4%) died within 1 year after hospitalisation of AECOPD; 32 of 51 genes differentially expressed in the prednisone cohort significantly changed from AECOPD to the convalescent state and were enriched in similar cellular immune pathways to that in the prednisone cohort. Of these, 10 genes including CX3CR1, KLRD1, S1PR5 and PRF1 were significantly associated with 1-year mortality. CONCLUSIONS: Short-term daily prednisone therapy produces a distinct blood gene signature that may be used to determine and monitor treatment responses to prednisone in COPD patients during AECOPD. TRIAL REGISTRATION: The prednisone cohort was registered at clinicalTrials.gov (NCT02534402) and the RTP cohort was registered at ClinicalTrials.gov (NCT02050022). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-019-1147-2) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6683462 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-66834622019-08-09 Effect of short-term oral prednisone therapy on blood gene expression: a randomised controlled clinical trial Takiguchi, Hiroto Chen, Virginia Obeidat, Ma’en Hollander, Zsuzsanna FitzGerald, J. Mark McManus, Bruce M. Ng, Raymond T. Sin, Don D. Respir Res Research BACKGROUND: Effects of systemic corticosteroids on blood gene expression are largely unknown. This study determined gene expression signature associated with short-term oral prednisone therapy in patients with chronic obstructive pulmonary disease (COPD) and its relationship to 1-year mortality following an acute exacerbation of COPD (AECOPD). METHODS: Gene expression in whole blood was profiled using the Affymetrix Human Gene 1.1 ST microarray chips from two cohorts: 1) a prednisone cohort with 37 stable COPD patients randomly assigned to prednisone 30 mg/d + standard therapy for 4 days or standard therapy alone and 2) the Rapid Transition Program (RTP) cohort with 218 COPD patients who experienced AECOPD and were treated with systemic corticosteroids. All gene expression data were adjusted for the total number of white blood cells and their differential cell counts. RESULTS: In the prednisone cohort, 51 genes were differentially expressed between prednisone and standard therapy group at a false discovery rate of < 0.05. The top 3 genes with the largest fold-changes were KLRF1, GZMH and ADGRG1; and 21 genes were significantly enriched in immune system pathways including the natural killer cell mediated cytotoxicity. In the RTP cohort, 27 patients (12.4%) died within 1 year after hospitalisation of AECOPD; 32 of 51 genes differentially expressed in the prednisone cohort significantly changed from AECOPD to the convalescent state and were enriched in similar cellular immune pathways to that in the prednisone cohort. Of these, 10 genes including CX3CR1, KLRD1, S1PR5 and PRF1 were significantly associated with 1-year mortality. CONCLUSIONS: Short-term daily prednisone therapy produces a distinct blood gene signature that may be used to determine and monitor treatment responses to prednisone in COPD patients during AECOPD. TRIAL REGISTRATION: The prednisone cohort was registered at clinicalTrials.gov (NCT02534402) and the RTP cohort was registered at ClinicalTrials.gov (NCT02050022). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-019-1147-2) contains supplementary material, which is available to authorized users. BioMed Central 2019-08-05 2019 /pmc/articles/PMC6683462/ /pubmed/31382977 http://dx.doi.org/10.1186/s12931-019-1147-2 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Takiguchi, Hiroto Chen, Virginia Obeidat, Ma’en Hollander, Zsuzsanna FitzGerald, J. Mark McManus, Bruce M. Ng, Raymond T. Sin, Don D. Effect of short-term oral prednisone therapy on blood gene expression: a randomised controlled clinical trial |
title | Effect of short-term oral prednisone therapy on blood gene expression: a randomised controlled clinical trial |
title_full | Effect of short-term oral prednisone therapy on blood gene expression: a randomised controlled clinical trial |
title_fullStr | Effect of short-term oral prednisone therapy on blood gene expression: a randomised controlled clinical trial |
title_full_unstemmed | Effect of short-term oral prednisone therapy on blood gene expression: a randomised controlled clinical trial |
title_short | Effect of short-term oral prednisone therapy on blood gene expression: a randomised controlled clinical trial |
title_sort | effect of short-term oral prednisone therapy on blood gene expression: a randomised controlled clinical trial |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683462/ https://www.ncbi.nlm.nih.gov/pubmed/31382977 http://dx.doi.org/10.1186/s12931-019-1147-2 |
work_keys_str_mv | AT takiguchihiroto effectofshorttermoralprednisonetherapyonbloodgeneexpressionarandomisedcontrolledclinicaltrial AT chenvirginia effectofshorttermoralprednisonetherapyonbloodgeneexpressionarandomisedcontrolledclinicaltrial AT obeidatmaen effectofshorttermoralprednisonetherapyonbloodgeneexpressionarandomisedcontrolledclinicaltrial AT hollanderzsuzsanna effectofshorttermoralprednisonetherapyonbloodgeneexpressionarandomisedcontrolledclinicaltrial AT fitzgeraldjmark effectofshorttermoralprednisonetherapyonbloodgeneexpressionarandomisedcontrolledclinicaltrial AT mcmanusbrucem effectofshorttermoralprednisonetherapyonbloodgeneexpressionarandomisedcontrolledclinicaltrial AT ngraymondt effectofshorttermoralprednisonetherapyonbloodgeneexpressionarandomisedcontrolledclinicaltrial AT sindond effectofshorttermoralprednisonetherapyonbloodgeneexpressionarandomisedcontrolledclinicaltrial |