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


RESULTS
Using 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.


CONCLUSIONS
Our 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.
Pulmonary Center, Boston University School of Medicine, Albany Street, Boston Massachusetts, USA. ssridhar@bu.edu
Sriram
S
Sridhar
Frank
F
Schembri
Julie
J
Zeskind
Vishal
V
Shah
Adam M
AM
Gustafson
Katrina
K
Steiling
Gang
G
Liu
Yves-Martine
YM
Dumas
Xiaohui
X
Zhang
Jerome S
JS
Brody
Marc E
ME
Lenburg
Avrum
A
Spira
D000328:Adult; D001980:Bronchi / Q000166:cytology / Q000378:metabolism*; D016022:Case-Control Studies; D004847:Epithelial Cells / Q000187:drug effects; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000166:cytology / Q000378:metabolism*; D009297:Nasal Mucosa / Q000166:cytology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D015203:Reproducibility of Results; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000235:genetics*; D014026:Nicotiana
D005819:Genetic Markers; D012906:Smoke