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Gene Expression in Lung Adenocarcinomas of Smokers and Nonsmokers

Department of Medicine, Columbia College of Physicians and Surgeons, New York, New York; Pulmonary Center and Department of Medicine, Boston University School of Medicine, and Bioinformatics Program, College of Engineering, Boston University, Boston, Massachusetts; Department of Pathology, Columbia University School of Medicine, New York, New York; Aventis Pharmaceuticals, Bridgewater, New Jersey; and Division of Thoracic Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts

Address correspondence to: Jerome S. Brody, M.D., Pulmonary Center R3, Boston University Medical Center, 715 Albany St., Boston, MA 02118. E-mail: jbrody{at}bu.edu

Adenocarcinoma (AC) has become the most frequent type of lung cancer in men and women, and is the major form of lung cancer in nonsmokers. Our goal in this paper was to determine if AC in smokers and nonsmokers represents the same genetic disease. We compared gene expression profiles in resected samples of nonmalignant lung tissue and tumor tissue in six never-smokers with AC and in six smokers with AC, who were matched for clinical staging and histologic criteria of cell differentiation. Results were analyzed using a variety of bioinformatic tools. Four times as many genes changed expression in the transition from noninvolved lung to tumor in nonsmokers as in smokers, suggesting that AC in nonsmokers evolves locally, whereas AC in smokers evolves in a field of genetically altered tissue. There were some similarities in gene expression in smokers and nonsmokers, but many differences, suggesting different pathways of cell transformation and tumor formation. Gene expression in the noninvolved lungs of smokers differed from that of nonsmokers, and multidimensional scaling showed that noninvolved lungs of smokers groups with tumors rather than noninvolved lungs of nonsmokers. In addition, expression of a number of genes correlated with smoking intensity. Our findings, although limited by small sample size, suggest that additional studies comparing noninvolved to tumor tissue may identify pathogenetic mechanisms and therapeutic targets that differ in AC of smokers and nonsmokers.

Abbreviations: adenocarcinoma, AC • multidimensional scaling, MDS • normal, N • nonsmoker normal, Nns • smoker normal, Ns • real-time polymerase chain reaction, QRT-PCR • tumor, T • transforming growth factor, TGF • nonsmoker tumor, Tns • smoker tumor, Ts

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