Transcriptomics

Dataset Information

3

ALTERATIONS IN THE SPUTUM PROTEOME AND TRANSCRIPTOME IN SMOKERS AND EARLY-STAGE COPD PATIENTS


ABSTRACT: Chronic obstructive pulmonary disease (COPD) is one of the most prevalent lung diseases, and involves persistent airflow limitation and incorporates both emphysema and chronic bronchitis. Cigarette smoking has been identified as the main risk factor for disease development and progression. In a basic model of COPD, the disease is initiated when the physiologic response mechanisms to cigarette smoke exposure are overwhelmed; for example, because of long-term exposure effects or other aging-related changes. In this parallel-group case-controlled clinical study we asked to what extent the different transitions in a chronic-exposure-to-disease model are reflected in the proteome and cellular transcriptome of induced sputum samples from the lung. For this, we selected 60 age- and gender-matched individuals for each of four study groups: current healthy smokers, current-smoker COPD patients, former smokers, and never smokers (a total of 240 individuals). Induced sputum was collected, the cell-free supernatant was analyzed by quantitative proteomics (isobaric-tag based), and the cellular mRNA fraction was analyzed by microarray-based expression profiling. The sputum proteome of current smokers (healthy or COPD patients) clearly reflected the common physiological responses to smoke exposure, including alterations in mucin/trefoil proteins (e.g., MUC5AC and TFF1/3up-regulation), peptidase regulators (e.g., TIMP1 up-regulation), and a prominent xenobiotic/oxidative stress response (e.g., NQO1 and ALDH3A1 up-regulation). The latter response also was observed in the sputum transcriptome, which additionally demonstrated an immune-related polarization change (toward a M2 signature). The (long-term) former smoker group showed nearly complete reversal of the observable biological effects. Thirteen differentially abundant proteins between the COPD and healthy smoker groups were identified. These abundant proteins included previously reported COPD-associated proteins (e.g., TIMP1 (up-regulation) and APOA1 (down-regulation)) and novel proteins such as C6orf58 and BPIFB1 (LPLUNC1) (both up-regulated in the COPD group compared with the healthy smokers). In summary, our study demonstrates that sputum proteomics/transcriptomics can capture the complex and reversible physiological response to cigarette smoke exposure, which appears to be only slightly modulated in early-stage COPD patients. The study has been registered on ClinicalTrials.gov with identifier NCT01780298.

INSTRUMENT(S): Affymetrix GeneChip(R) HT Scanner

ORGANISM(S): Homo sapiens  

SUBMITTER: Emmanuel Guedj   Sam Ansari   Alain Sewer   Nveed Chaudhary  

PROVIDER: E-MTAB-3604 | ArrayExpress | 2015-08-28

REPOSITORIES: ArrayExpress

Similar Datasets

2016-10-21 | MSV000080275 | Massive
| GSE8987 | GEO
2008-10-20 | E-GEOD-8987 | ArrayExpress
| GSE19667 | GEO
2009-01-29 | GSE14634 | GEO
| GSE18033 | GEO
| GSE17737 | GEO
| GSE5058 | GEO
2014-07-02 | E-GEOD-55962 | ArrayExpress
2009-01-28 | E-GEOD-14634 | ArrayExpress