title: Current smoking-specific gene expression signature in normal bronchial epithelium is enhanced in squamous cell lung cancer.
abstract: Cigarette smoking is the main risk factor for the development of squamous cell lung carcinoma (SCC). However, the smoking-related molecular changes in SCC have not been studied. Gene expression studies in both histologically normal bronchial epithelium and SCC epithelial samples identified genes differentially expressed between current and ex-smokers. Subsequently, expression levels of the smoking-related genes in normal bronchial epithelium were compared with those in SCC cells, since we hypothesized that the smoking-induced changes would be also deregulated in SCC. Gene expression profiles were generated using Agilent whole human genome microarrays on laser-microdissected normal bronchial epithelium and SCC samples. Expression levels of 246 genes, mainly related to oxidative stress response, were significantly different between normal bronchial epithelium of current and ex-smokers. Such a differential gene expression profile did not exist in SCC cells of smokers and ex-smokers. Interestingly, when comparing SCC and normal bronchial epithelium from ex-smokers, the vast majority of these 246 genes were also deregulated in SCC. When comparing SCC with normal epithelium from smokers, 22% of the up-regulated genes showed a similar high expression in SCC whereas 79% of the down-regulated genes were even further reduced in SCC as compared to current smokers. The down-regulated genes included several tumour suppressor genes, such as C9orf9, INHBB, LRIG1, SCGB3A1, SERPINI2, STEAP3 and ZMYND10. Thus, our study shows that the majority of genes up-regulated in normal bronchial epithelium of current smokers show similar high expression levels in SCC, while down-regulated genes are even further repressed in SCC. Our data indicate that smoking-related changes in normal bronchial epithelial cells persist in malignant transformed squamous cells.
authors.affiliation: Department of Pathology, University Medical Centre Groningen, Groningen, The Netherlands.
authors.forename: Mirjam C
authors.initials: MC
authors.lastname: Boelens
authors.forename: Anke
authors.initials: A
authors.lastname: van den Berg
authors.forename: Rudolf S N
authors.initials: RS
authors.lastname: Fehrmann
authors.forename: Marie
authors.initials: M
authors.lastname: Geerlings
authors.forename: Wouter K
authors.initials: WK
authors.lastname: de Jong
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: te Meerman
authors.forename: Hannie
authors.initials: H
authors.lastname: Sietsma
authors.forename: Wim
authors.initials: W
authors.lastname: Timens
authors.forename: Dirkje S
authors.initials: DS
authors.lastname: Postma
authors.forename: Harry J M
authors.initials: HJ
authors.lastname: Groen