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| Status |
Public on Jul 01, 2018 |
| Title |
Expression data from lung tissue in mild-moderate COPD |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Rationale: Chronic Obstructive Pulmonary Disease (COPD) is associated with a complex pulmonary and systemic immune response.
Objective: To characterize and relate the lung tissue and circulating blood network immune response in COPD.
Methods: Lung tissue and circulating blood samples were simultaneously obtained from COPD patients (current smokers n=28 and former smokers n=16) and controls (current smokers n=9 and non-smokers n=12) undergoing thoracic surgery. We used flow cytometry to assess the immune cell composition, Affymetrix arrays to determine whole lung mRNA expression, and Weighted Gene Co-expression Network Analysis (WGCNA) to characterize and compare the pulmonary and systemic immune responses in patients and controls.
Results: In lung tissue of current smokers with COPD (vs. non-smokers and former smokers with COPD) we observed a significant increase in the proportion of intermediated phenotype macrophages (Mphage) expressing both M1 and M2 markers, whereas that of M1 Mphage (pro-inflammatory) and CD4+ and CD8+ T-lymphocytes were decreased. These changes were not mirrored in circulating blood but WGCNA identified three modules of co-expressed genes that related, respectively to: (1) the total proportion of lung Mphage (extracellular matrix and angiogenesis genes) ; (2) active smoking (T cell and apoptosis related genes); and, (3) severity of airflow limitation (cilium organization genes).
Conclusions: In mild/moderate COPD, the main pulmonary immune cell alterations relate to current smoking, involve changes in the proportion of Mphage and T cells and are associated with changes in whole lung tissue transcriptome. These cellular pulmonary changes are not mirrored in the systemic circulation.
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| Overall design |
Fresh lung tissue was preserved in RNAlater® (Life Technologies, US). From 53 individuals, total RNA was isolated with PureLink RNA-MiniKit (Life Technologies, US), quantified by Nanodrop (Thermo Scientific, Germany). RNA samples with integrity numbers (RIN) ≥ 7 (Agilent technologies, Germany), where analyzed with the Affymetrix GeneChip® Human Genome U219 Array Plate at the IDIBAPS genomics platform. Microarray results were RMA normalized and probes in the lowest quartile of variability were removed. Remaining probes were then collapsed to gene Symbols and a weighted gene co-expression network (WGNCA) was built with soft thresholding power of 9, on a total of 53 individuals. The analysis produced 24 modules, each containing a set of unique genes. Module eigengenes were correlated with variables of interest (FEV1, Smoking status, Lung Monocytes, Lung T Lymphocytes, macrophages and BMI).
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| Contributor(s) |
Cruz T, López-Giraldo A, Noell G, Casas-Recasens S, Garcia T, Molins L, Juan M, Fernandez MA, Agustí A, Faner R |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Aug 28, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Guillaume Noell |
| Organization name |
CIBER Enfermedades Respiratorias, Grupo 10, IDIBAPS-Fundació Privada Clínic de Barcelona
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| Lab |
Cellex P2A
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| Street address |
C/Casanova 143
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| City |
BARCELONA |
| ZIP/Postal code |
08036 |
| Country |
Spain |
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| Platforms (1) |
| GPL13667 |
[HG-U219] Affymetrix Human Genome U219 Array |
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| Samples (53)
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| Relations |
| BioProject |
PRJNA400447 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE103174_RAW.tar |
112.6 Mb |
(http)(custom) |
TAR (of CEL) |
| GSE103174_log2RMAsignals_genesymbols.txt.gz |
4.4 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
| Processed data are available on Series record |
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