Similarities and differences between smoking-related gene expression in nasal and bronchial epithelium

Abstract

Previous studies have shown that physiological responses to cigarette smoke can be detected via bronchial airway epithelium gene expression profiling and that heterogeneity in this gene expression response to smoking is associated with lung cancer. In this study, we sought to determine the similarity of the effects of tobacco smoke throughout the respiratory tract by determining patterns of smoking-related gene expression in paired nasal and bronchial epithelial brushings collected from 14 healthy nonsmokers and 13 healthy current smokers. Using whole genome expression arrays, we identified 119 genes whose expression was affected by smoking similarly in both bronchial and nasal epithelium, including genes related to detoxification, oxidative stress, and wound healing. While the vast majority of smoking-related gene expression changes occur in both bronchial and nasal epithelium, we also identified 27 genes whose expression was affected by smoking more dramatically in bronchial epithelium than nasal epithelium. Both common and site-specific smoking-related gene expression profiles were validated using independent microarray datasets. Differential expression of select genes was also confirmed by RT-PCR. That smoking induces largely similar gene expression changes in both nasal and bronchial epithelium suggests that the consequences of cigarette smoke exposure can be measured in tissues throughout the respiratory tract. Our findings suggest that nasal epithelial gene expression may serve as a relatively noninvasive surrogate to measure physiological responses to cigarette smoke and/or other inhaled exposures in large-scale epidemiological studies.

Personalized Management of Chronic Obstructive Pulmonary Disease via Transcriptomic Profiling of the Airway and Lung

“…Airway epithelial cells represent a promising biospecimen for studying COPD, as molecular profiles in minimally invasively collected tissue specimens will be needed if these biomarkers are to ultimately translate into the clinic. Beyond the potential of bronchial epithelium, which we have highlighted in this review, recent work suggests that gene expression signatures in nasal and buccal epithelium may serve as surrogates for the bronchial airway response to cigarette smoke (29,30), and future studies should evaluate whether COPDassociated gene expression changes can also be identified at these readily accessible sites. Technologic advances, such as single-cell sequencing (51), also hold the potential to improve characterization of disease heterogeneity by providing a detailed portrait of disease-associated processes occurring in different cell types within a tissue and the heterogeneity of those processes between different cells of the same cell type.…”

“…The airway field of injury hypothesis, initially established in the setting of cigarette smoke exposure, posits that toxins and carcinogens from cigarette smoke bathe the entire respiratory tract. This exposure leads to measurable alterations in the small airway epithelium (28), large airway epithelium (27), and epithelium of the nose and mouth (29,30). A diseasespecific airway field of injury has been described in the setting of lung cancer, where gene expression profiling of the cytologically normal airway epithelium distal from the lung tumor can serve as a sensitive and specific biomarker of lung cancer (31) that performs independently of other clinical variables (32).…”

Bronchialkarzinomscreening – Risikostratifizierung

“…Derzeit ist jedoch noch keiner dieser Biomarker oder Risikogene zur klinischen Anwendung geeignet [10]. Experimentelle Ansätze konnten zeigen, dass Genanalysen des Nasalepithels von Rauchern als Surrogatparameter dienen könnten, um den schadhaften Effekt des Rauchens auf die Lunge zu beurteilen [30]. Die Entwicklung von Biomarkern und Risikogenen tritt somit zunehmend in den Fokus der Forschung, und die laufenden Screeningstudien könnten beitragen, hier in den kommenden Jahre weitere Fortschritte zu erzielen [8,9].…”

Upper Airway Gene Expression in Smokers: The Mouth as a “Window to the Soul” of Lung Carcinogenesis?

“…Bhutani et al further supported this conclusion when they found a strong correlation between bronchial and oral tissue in the degree of p16 and FHIT promoter methylation at baseline and 3 months after intervention in 127 smokers enrolled in a randomized placebo-controlled chemoprevention trial (18,19); this rather specific study, however, did not profile global epigenetic changes in the bronchi and oral cavity. More recent analyses of genome-wide gene expression profiling of matched nasal and bronchial epithelium showed that the majority of gene expression consequences of smoking are common to both nasal and bronchial epithelium, suggesting that nasal epithelial gene expression may serve as a relatively noninvasive surrogate measure of physiologic responses to cigarette smoke in the lower airway (20).…”

“…Genomic profiling of matched upper and lower airway cells from the same individual (versus from unrelated individuals) is needed to fully characterize the ability of the mouth to serve as a surrogate for the bronchus (18,20). Further study of buccal sampling methods is also needed.…”