title: Lung adenocarcinoma subtypes based on expression of human airway basal cell genes.
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.
authors: Weill Cornell Medical College, New York, NY.
authors: Tomoya
authors: T
authors: Fukui
authors: Renat
authors: R
authors: Shaykhiev
authors: Francisco
authors: F
authors: Agosto-Perez
authors: Jason G
authors: JG
authors: Mezey
authors: Robert J
authors: RJ
authors: Downey
authors: William D
authors: WD
authors: Travis
authors: Ronald G
authors: RG
authors: Crystal
mesh_terms: D000230:Adenocarcinoma / Q000145:classification* / Q000235:genetics* / Q000401:mortality; D000077192:Adenocarcinoma of Lung; D000368:Aged; D001706:Biopsy; D002454:Cell Differentiation; D015331:Cohort Studies; D004847:Epithelial Cells / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000145:classification* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D018295:Neoplasms, Basal Cell / Q000378:metabolism*; D010641:Phenotype; D025341:Principal Component Analysis; D016016:Proportional Hazards Models; D059467:Transcriptome; D018631:ras Proteins / Q000235:genetics
chemical_list: D066246:ErbB Receptors; D018631:ras Proteins
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