Global gene expression differentiating pure bronchioloalveolar carcinoma from adenocarcinoma with bronchioloalveolar carcinoma features

Abstract

Objectives: Pure bronchioloalveolar carcinoma (BAC) is considered the early stage of lung adenocarcinoma, and is even regarded as lung adenocarcinoma in situ. This study was designed to investigate the differences in the gene expression of pure BAC and that of adenocarcinoma with bronchioloalveolar features and explore the mechanism of BAC progression to adenocarcinoma with bronchioloalveolar features Methods: Total RNA was extracted from 16 tissue specimens. Expression analysis was carried out using Agilent 4 × 44 k arrays. Gene ontology analysis was used to define pathways altered in bronchioloalveolar progression. Differentially expressed candidate genes were validated using quantitative real-time PCR. The statistical analysis was carried out according to the methods of the paired t-test. Results: Adenocarcinoma with bronchioloalveolar features demonstrated an increased expression of 23 genes and reduced expression of 20 genes compared with BAC. These genes were considered candidate marker genes for tumour progression and metastasis. Genes overexpressed in adenocarcinoma with bronchioloalveolar features included fibroblast growth factor receptor 1, and CLDN18 (claudin 18), whereas those overexpressed in BAC included ataxia telangiectasia and Rad3 related (ataxia telangiectasia mutated and Rad3- related), and activating transcription factor 2. Mitogen-activated protein kinase (MAPK) pathway seemed dysregulated in adenocarcinoma with bronchioloalveolar features compared with pure BAC. Conclusions: Microarray-based expression profiling revealed interesting novel candidate genes in BAC and adenocarcinoma with bronchioloalveolar features. The MAPK pathway seemed dysregulated in adenocarcinoma with bronchioloalveolar features compared with the pure BAC pathway, which is worthy of being explored because it could partially explain the mechanism of the progression of BAC to adenocarcinoma with bronchioloalveolar features. © The Author 2012. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.