Publication Type	Academic Article
Authors	Fukui T, Shaykhiev R, Agosto-Perez F, Mezey J, Downey R, Travis W, Crystal R
Journal	Eur Respir J
Volume	42
Issue	5
Pagination	1332-44
Date Published	05/03/2013
ISSN	1399-3003
Keywords	Adenocarcinoma, Lung Neoplasms, Neoplasms, Basal Cell
Abstract	Lung cancer, including lung adenocarcinoma, is a heterogeneous disease, which evolves from molecular alterations in the airway epithelium. This study explores whether a subtype of lung adenocarcinomas expresses the unique molecular features of human airway basal cells (BCs), and how expression of the airway BC features correlates with the molecular, pathological and clinical phenotype of lung adenocarcinoma. Three independent lung adenocarcinoma data sets were analysed for expression of genes that constitute the airway BC signature. Expression of the BC signature in lung adenocarcinoma was then correlated to clinical and biological parameters. Remarkable enrichment of airway BC signature genes was found in lung adenocarcinomas. A subset of lung adenocarcinomas (BC-high adenocarcinoma) exhibited high expression of BC signature genes in association with poorer tumour grade, higher frequency of vascular invasion and shorter survival than adenocarcinomas with lower expression of these genes. At the molecular level, BC-high adenocarcinomas displayed a higher frequency of KRAS mutations, activation of transcriptional networks and pathways related to cell cycle, extracellular matrix organisation, and a distinct differentiation pattern with suppression of ciliated and exocrine bronchiolar cell (Clara cell)-related genes. Activation of the airway BC programme is a molecular feature of a distinct, aggressive subtype of lung adenocarcinoma.
DOI	10.1183/09031936.00144012
PubMed ID	23645403
PubMed Central ID	PMC4124529