title: Airway basal cells of healthy smokers express an embryonic stem cell signature relevant to lung cancer.
abstract: 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 pattern 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 adenocarcinoma (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 considerable 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 evidence that smoking-induced reprogramming of airway BC toward the hESC-like phenotype might represent a common early molecular event in the development of aggressive lung carcinomas in humans.
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Renat
authors.initials: R
authors.lastname: Shaykhiev
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Rachel K
authors.initials: RK
authors.lastname: Zwick
authors.forename: Neil R
authors.initials: NR
authors.lastname: Hackett
authors.forename: Roland
authors.initials: R
authors.lastname: Leung
authors.forename: Malcolm A S
authors.initials: MA
authors.lastname: Moore
authors.forename: Camelia S
authors.initials: CS
authors.lastname: Sima
authors.forename: Ion Wa
authors.initials: IW
authors.lastname: Chao
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Downey
authors.forename: Yael
authors.initials: Y
authors.lastname: Strulovici-Barel
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Salit
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Crystal
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000818:Animals; D045744:Cell Line, Tumor; D053595:Embryonic Stem Cells / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D015999:Multivariate Analysis; D010641:Phenotype; D016016:Proportional Hazards Models; D012907:Smoking / Q000235:genetics* / Q000473:pathology*; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53
keywords: Airway epithelium; Basal cells; Gene expression; Lung cancer; Stem cells