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Effect of Smoking and Its Cessation on the Transcript Profile of Peripheral Monocytes in COPD Patients

RATIONALE: Smoking is the primary cause of chronic obstructive pulmonary disease (COPD); however, only 10–20% of smokers develop the disease suggesting possible genomic association in the causation of the disease. In the present study, we aimed to explore the whole genome transcriptomics of blood mo...

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Autores principales: Trivedi, Anjali, Bade, Geetanjali, Madan, Karan, Ahmed Bhat, Muzaffer, Guleria, Randeep, Talwar, Anjana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8749770/
https://www.ncbi.nlm.nih.gov/pubmed/35027824
http://dx.doi.org/10.2147/COPD.S337635
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author Trivedi, Anjali
Bade, Geetanjali
Madan, Karan
Ahmed Bhat, Muzaffer
Guleria, Randeep
Talwar, Anjana
author_facet Trivedi, Anjali
Bade, Geetanjali
Madan, Karan
Ahmed Bhat, Muzaffer
Guleria, Randeep
Talwar, Anjana
author_sort Trivedi, Anjali
collection PubMed
description RATIONALE: Smoking is the primary cause of chronic obstructive pulmonary disease (COPD); however, only 10–20% of smokers develop the disease suggesting possible genomic association in the causation of the disease. In the present study, we aimed to explore the whole genome transcriptomics of blood monocytes from COPD smokers (COPD-S), COPD Ex-smokers (COPD-ExS), Control smokers (CS), and Control Never-smokers (CNS) to understand the differential effects of smoking, COPD and that of smoking cessation. METHODS: Exploratory analyses in form of principal component analysis (PCA) and hierarchical component analysis (uHCA) were performed to evaluate the similarity in gene expression patterns, while differential expression analyses of different supervised groups of smokers and never smokers were performed to study the differential effect of smoking, COPD and smoking cessation. Differentially expressed genes among groups were subjected to post-hoc enrichment analysis. Candidate genes were subjected to external validation by quantitative RT-PCR experiments. RESULTS: CNS made a cluster completely segregated from the other three subgroups (CS, COPDS and COPD-ExS). About 550, 8 and 5 genes showed differential expression, respectively, between CNS and CS, between CS and COPD-S, and between COPD-S and COPD-ExS. Apoptosis, immune response, cell adhesion, and inflammation were the top process networks identified in enrichment analysis. Two candidate genes (CASP9 and TNFRSF1A) found to be integral to several pathways in enrichment analysis were validated in an external validation experiment. CONCLUSION: Control never smokers had formed a cluster distinctively separated from all smokers (COPDS, COPD-ExS, and CS), while amongst all smokers, control smokers had aggregated in a separate cluster. Smoking cessation appeared beneficial if started at an early stage as many genes altered due to smoking started reverting towards the baseline, whereas only a few COPD-related genes showed reversal after smoking cessation.
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spelling pubmed-87497702022-01-12 Effect of Smoking and Its Cessation on the Transcript Profile of Peripheral Monocytes in COPD Patients Trivedi, Anjali Bade, Geetanjali Madan, Karan Ahmed Bhat, Muzaffer Guleria, Randeep Talwar, Anjana Int J Chron Obstruct Pulmon Dis Original Research RATIONALE: Smoking is the primary cause of chronic obstructive pulmonary disease (COPD); however, only 10–20% of smokers develop the disease suggesting possible genomic association in the causation of the disease. In the present study, we aimed to explore the whole genome transcriptomics of blood monocytes from COPD smokers (COPD-S), COPD Ex-smokers (COPD-ExS), Control smokers (CS), and Control Never-smokers (CNS) to understand the differential effects of smoking, COPD and that of smoking cessation. METHODS: Exploratory analyses in form of principal component analysis (PCA) and hierarchical component analysis (uHCA) were performed to evaluate the similarity in gene expression patterns, while differential expression analyses of different supervised groups of smokers and never smokers were performed to study the differential effect of smoking, COPD and smoking cessation. Differentially expressed genes among groups were subjected to post-hoc enrichment analysis. Candidate genes were subjected to external validation by quantitative RT-PCR experiments. RESULTS: CNS made a cluster completely segregated from the other three subgroups (CS, COPDS and COPD-ExS). About 550, 8 and 5 genes showed differential expression, respectively, between CNS and CS, between CS and COPD-S, and between COPD-S and COPD-ExS. Apoptosis, immune response, cell adhesion, and inflammation were the top process networks identified in enrichment analysis. Two candidate genes (CASP9 and TNFRSF1A) found to be integral to several pathways in enrichment analysis were validated in an external validation experiment. CONCLUSION: Control never smokers had formed a cluster distinctively separated from all smokers (COPDS, COPD-ExS, and CS), while amongst all smokers, control smokers had aggregated in a separate cluster. Smoking cessation appeared beneficial if started at an early stage as many genes altered due to smoking started reverting towards the baseline, whereas only a few COPD-related genes showed reversal after smoking cessation. Dove 2022-01-05 /pmc/articles/PMC8749770/ /pubmed/35027824 http://dx.doi.org/10.2147/COPD.S337635 Text en © 2022 Trivedi et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Trivedi, Anjali
Bade, Geetanjali
Madan, Karan
Ahmed Bhat, Muzaffer
Guleria, Randeep
Talwar, Anjana
Effect of Smoking and Its Cessation on the Transcript Profile of Peripheral Monocytes in COPD Patients
title Effect of Smoking and Its Cessation on the Transcript Profile of Peripheral Monocytes in COPD Patients
title_full Effect of Smoking and Its Cessation on the Transcript Profile of Peripheral Monocytes in COPD Patients
title_fullStr Effect of Smoking and Its Cessation on the Transcript Profile of Peripheral Monocytes in COPD Patients
title_full_unstemmed Effect of Smoking and Its Cessation on the Transcript Profile of Peripheral Monocytes in COPD Patients
title_short Effect of Smoking and Its Cessation on the Transcript Profile of Peripheral Monocytes in COPD Patients
title_sort effect of smoking and its cessation on the transcript profile of peripheral monocytes in copd patients
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8749770/
https://www.ncbi.nlm.nih.gov/pubmed/35027824
http://dx.doi.org/10.2147/COPD.S337635
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