Smoking-induced gene expression changes in the bronchial airway are reflected in nasal and buccal epithelium.

Sriram Sridhar,Avrum Spira,Katrina Steiling,Vishal Shah,Jerome S Brody,Gang Liu,Marc E Lenburg,Yves-Martine Dumas,Julie Zeskind,Frank Schembri,Adam M Gustafson,Xiaohui Zhang

doi:10.1186/1471-2164-9-259

Abstract

BackgroundCigarette smoking is a leading cause of preventable death and a significant cause of lung cancer and chronic obstructive pulmonary disease. Prior studies have demonstrated that smoking creates a field of molecular injury throughout the airway epithelium exposed to cigarette smoke. We have previously characterized gene expression in the bronchial epithelium of never smokers and identified the gene expression changes that occur in the mainstem bronchus in response to smoking. In this study, we explored relationships in whole-genome gene expression between extrathorcic (buccal and nasal) and intrathoracic (bronchial) epithelium in healthy current and never smokers.ResultsUsing genes that have been previously defined as being expressed in the bronchial airway of never smokers (the "normal airway transcriptome"), we found that bronchial and nasal epithelium from non-smokers were most similar in gene expression when compared to other epithelial and nonepithelial tissues, with several antioxidant, detoxification, and structural genes being highly expressed in both the bronchus and nose. Principle component analysis of previously defined smoking-induced genes from the bronchus suggested that smoking had a similar effect on gene expression in nasal epithelium. Gene set enrichment analysis demonstrated that this set of genes was also highly enriched among the genes most altered by smoking in both nasal and buccal epithelial samples. The expression of several detoxification genes was commonly altered by smoking in all three respiratory epithelial tissues, suggesting a common airway-wide response to tobacco exposure.ConclusionOur findings support a relationship between gene expression in extra- and intrathoracic airway epithelial cells and extend the concept of a smoking-induced field of injury to epithelial cells that line the mouth and nose. This relationship could potentially be utilized to develop a non-invasive biomarker for tobacco exposure as well as a non-invasive screening or diagnostic tool providing information about individual susceptibility to smoking-induced lung diseases.

Highlights

Cigarette smoking is a leading cause of preventable death and a significant cause of lung cancer and chronic obstructive pulmonary disease
Using epithelial cells collected from brushings of the mainstem bronchus at the time of bronchoscopy, we have previously characterized the effect of smoking on the bronchial airway epithelial transcriptome and found that smoking induces expression of genes involved in regulation of oxidant stress, xenobiotic metabolism, and oncogenesis while suppressing those involved in regulation of inflammation and tumor suppression [8]
Our results suggest that gene expression changes occurring in bronchial epithelium in response to cigarette smoke are reflected in buccal and nasal epithelium

Summary

Introduction

Cigarette smoking is a leading cause of preventable death and a significant cause of lung cancer and chronic obstructive pulmonary disease. We recently developed a profile of bronchial airway gene expression that can distinguish smokers with and without lung cancer and serve as an early diagnostic biomarker for disease [9]. These studies of intrathoracic airway epithelium obtained via bronchoscopy have successfully identified candidate biomarkers of smoking-related lung damage, there remains significant impetus to develop biomarkers of these events from tissue obtained via less invasive collection procedures. Use of material from a less invasive collection site would allow for the use of larger cohorts for developing and validating biomarkers of tobacco exposure and susceptibility to tobacco-related disease

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Conclusion