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(Chest. 2004;125:115S.)
© 2004 American College of Chest Physicians

Impact of Cigarette Smoke on the Normal Airway Transcriptome*

Avrum Spira, MD; Frank Schembri, MD; Jennifer Beane; Vishal Shah; Gang Liu, PhD and Jerome S. Brody, MD

* From The Pulmonary Center, Boston University School of Medicine (Drs. Spira, Schembri, Liu, and Brody); and the Bioinformatics Program, Boston University, Boston, MA (Dr. Spira, Ms. Beane, and Mr. Shah).

Correspondence to: Avrum Spira, MD, The Pulmonary Center, 715 Albany St, R3, Boston, MA 02118-2526; e-mail: aspira{at}lung bumc.bu.edu

It is unclear whether all smokers respond at a molecular level to cigarette smoke in the same fashion or whether smokers destined to develop cancer display early changes in gene expression that are premalignant in nature. Several studies12 have shown that smoking produces a "field defect" in the lung and its airways, such that molecular changes occur throughout the respiratory tract. To determine whether the molecular field defect is similar in all smokers, we have begun a study of gene expression profiles of airway epithelial cells obtained during bronchoscopy from normal nonsmokers and compared the airway transcriptome to that in smokers without cancer.

Fiberoptic bronchoscopy was performed in 15 normal nonsmokers and in 15 smokers without cancer. The right upper lobe carina was brushed, and RNA was extracted and processed (U133A Genechip; Affymetrix; Santa Clara, CA) [approximately 22,500 genes]. Filter criteria for the quality of a sample were developed, and data were analyzed using a variety of computational algorithms. In nonsmokers, the variation in the expression level of genes among subjects was small. Multiple linear regression revealed that age, sex, and race had little effect on the nonsmoker transcriptome, as < 2% of the gene expression levels were associated with any of these three variables at the p < 0.01 level. Using a t test, 206 genes (4%) differed between smokers and nonsmokers at p < 0.01, and 610 genes differed at p < 0.05. The greatest increases in smokers occurred in genes associated with cell adhesion, detoxification, and secretion. The greatest decreases were in immune-regulatory genes and cytokeratins, with the decrease in the latter suggesting a change in epithelial cell differentiation. Linear regression analysis showed that the expression of 95 genes correlated (p < 0.01, R >= 0.6) with the number of pack-years of smoking in smokers.

These preliminary results have begun to define the gene expression profile of the normal human airway and to characterize the impact of cigarette smoking on the airway transcriptome. Our ultimate goal is to determine whether the transcriptome will identify early markers in those smokers who develop lung cancer.


   Footnotes
 
This research was supported in part by grants HL71771 and ES10377 from Affymetrix, and by a Doris Duke Clinical Scientist Development Award (to AS).


   References
TOP
 References
 

  1. Wistuba, II, Lam, S, Behrens, C, et al (1997) Molecular damage in the bronchial epithelium of current and former smokers. J Natl Cancer Inst 89,1366-1373[Abstract/Free Full Text]
  2. Powell, CA, Spira, A, Derti, A, et al Gene expression in lung adenocarcinomas of smokers and nonsmokers. Am J Respir Cell Mol Biol 2003;29,157-162[Abstract/Free Full Text]




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