Molecular characterization of the peripheral airway field of cancerization in lung adenocarcinoma

PLoS One. 2015 Feb 23;10(2):e0118132. doi: 10.1371/journal.pone.0118132. eCollection 2015.

Abstract

Field of cancerization in the airway epithelium has been increasingly examined to understand early pathogenesis of non-small cell lung cancer. However, the extent of field of cancerization throughout the lung airways is unclear. Here we sought to determine the differential gene and microRNA expressions associated with field of cancerization in the peripheral airway epithelial cells of patients with lung adenocarcinoma. We obtained peripheral airway brushings from smoker controls (n=13) and from the lung contralateral to the tumor in cancer patients (n=17). We performed gene and microRNA expression profiling on these peripheral airway epithelial cells using Affymetrix GeneChip and TaqMan Array. Integrated gene and microRNA analysis was performed to identify significant molecular pathways. We identified 26 mRNAs and 5 miRNAs that were significantly (FDR <0.1) up-regulated and 38 mRNAs and 12 miRNAs that were significantly down-regulated in the cancer patients when compared to smoker controls. Functional analysis identified differential transcriptomic expressions related to tumorigenesis. Integration of miRNA-mRNA data into interaction network analysis showed modulation of the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) pathway in the contralateral lung field of cancerization. In conclusion, patients with lung adenocarcinoma have tumor related molecules and pathways in histologically normal appearing peripheral airway epithelial cells, a substantial distance from the tumor itself. This finding can potentially provide new biomarkers for early detection of lung cancer and novel therapeutic targets.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Aged
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Epithelial Cells / metabolism
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Gene Expression Profiling*
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / genetics*
  • Respiratory System / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Smoking

Substances

  • MicroRNAs
  • RNA, Messenger
  • Extracellular Signal-Regulated MAP Kinases

Associated data

  • GEO/GSE54495
  • GEO/GSE54541