Lung adenocarcinoma subtypes based on expression of human airway basal cell genes Academic Article uri icon

Overview

MeSH Major

  • 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.

publication date

  • November 2013

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4124529

Digital Object Identifier (DOI)

  • 10.1183/09031936.00144012

PubMed ID

  • 23645403

Additional Document Info

start page

  • 1332

end page

  • 44

volume

  • 42

number

  • 5