Airway Basal Cells of Healthy Smokers Express an Embryonic Stem Cell Signature Relevant to Lung Cancer

Activation of the human embryonic stem cell (hESC)-signature genes has been observed in various epithelial cancers. In this study, we found that the hESC signature is selectively induced in the airway basal stem/progenitor cell population of healthy smokers (BC-S), with a pat-tern similar to that activated in all major types of human lung cancer. We further identified a subset of 6 BC-S hESC genes, whose coherent overexpression in lung AdCa was associated with reduced lung function, poorer differentiation grade, more advanced tumor stage, remarkably shorter survival and higher frequency of TP53 mutations. BC-S shared with hESC and a consid-erable subset of lung carcinomas a common TP53 inactivation molecular pattern which strongly correlated with the BC-S hESC gene expression. These data provide transcriptome-based evi-dence that smoking-induced reprogramming of airway BC towards the hESC-like phenotype might represent a common early molecular event in the development of aggressive lung carci-nomas in humans. Affymetrix arrays were used to assess gene expression data of genes realted to human embryonic stem cells in large airway epithelium obtained by fiberoptic bronchoscopy of 21 healthy non-smokers and 31 healthy smokers, basal cell culture of large airway epithelium obtained by fiberoptic bronchoscopy of 4 healthy nonsmokers and 4 healthy smokers and cells obtained from tumor tissues of 4 individuals.