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Lung adenocarcinoma subtypes based on expression of human airway basal cell genes.
- Source :
-
The European respiratory journal [Eur Respir J] 2013 Nov; Vol. 42 (5), pp. 1332-44. Date of Electronic Publication: 2013 May 03. - Publication Year :
- 2013
-
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.
- Subjects :
- Adenocarcinoma mortality
Adenocarcinoma of Lung
Aged
Biopsy
Cell Differentiation
Cohort Studies
Epithelial Cells pathology
ErbB Receptors genetics
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Lung Neoplasms mortality
Male
Middle Aged
Phenotype
Principal Component Analysis
Proportional Hazards Models
Transcriptome
ras Proteins genetics
Adenocarcinoma classification
Adenocarcinoma genetics
Lung Neoplasms classification
Lung Neoplasms genetics
Neoplasms, Basal Cell metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1399-3003
- Volume :
- 42
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- The European respiratory journal
- Publication Type :
- Academic Journal
- Accession number :
- 23645403
- Full Text :
- https://doi.org/10.1183/09031936.00144012