Gene expression profile of epithelial-mesenchymal transition in tumours of patients with nonsmall cell lung cancer

Epithelial-mesenchymal transition (EMT) is involved in the pathophysiology of lung cancer (LC) and COPD, and the latter is an important risk factor for LC. We hypothesised that the EMT gene expression profile and signalling cascade may differ in LC patients with COPD from those with no respiratory d...

ver descrição completa

Detalhes bibliográficos
Autores: Xia, Yingchen|||0000-0001-5697-7222, Zha, Jianhua, Curull Serrano, Víctor|||0000-0003-2709-7431, Sánchez Font, Albert|||0000-0003-1026-7908, Guitart, Maria|||0000-0003-2957-7404, Rodríguez-Fuster, Alberto|||0000-0002-4900-6126, Aguiló Espases, Rafael, Barreiro, Esther|||0000-0003-2708-3443
Formato: artículo
Fecha de publicación:2022
País:España
Recursos:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:282448
Acesso em linha:https://ddd.uab.cat/record/282448
https://dx.doi.org/urn:doi:10.1183/23120541.00105-2022
Access Level:acceso abierto
Descrição
Resumo:Epithelial-mesenchymal transition (EMT) is involved in the pathophysiology of lung cancer (LC) and COPD, and the latter is an important risk factor for LC. We hypothesised that the EMT gene expression profile and signalling cascade may differ in LC patients with COPD from those with no respiratory diseases. In lung tumour specimens obtained through video-assisted thoracoscopic surgery from LC (n=20, control group) and LC-COPD patients (n=30), gene expression (quantitative real-time PCR amplification) of EMT markers SMAD3, SMAD4, ZEB2, TWIST1, SNAI1, ICAM1, VIM, CDH2, MMP1 and MMP9 was detected. In lung tumours of LC-COPD compared to LC patients, gene expression of SMAD3, SMAD4, ZEB2 and CDH2 significantly declined, while no significant differences were detected for the other analysed markers. A significant correlation was found between pack-years (smoking burden) and SMAD3 gene expression among LC-COPD patients. LC-COPD patients exhibited mild-to-moderate airway obstruction and a significant reduction in diffusion capacity compared to LC patients. In lung tumour samples of patients with COPD, several markers of EMT expression, namely SMAD3, SMAD4, ZEB2 and CDH2, were differentially expressed suggesting that these markers are likely to play a role in the regulation of EMT in patients with this respiratory disease. Cigarette smoke did not seem to influence the expression of EMT markers in this study. These results have potential clinical implications in the management of patients with LC, particularly in those with underlying respiratory diseases. The downregulation of the epithelial-mesenchymal transition repressor SMAD pathway may favour a pro-tumoural micro-environment in patients with chronic airway diseases, namely COPD, which could be targeted therapeutically.