Introduction: Our previous studies have shown active EMT in smokers and COPD patients, which is central to lung cancer development in these patients. 

Aim: We aim to evaluate EMT changes in extensive patient groups who were diagnosed with NSCLC (adenocarcinoma and squamous cell carcinoma) compared to normal controls (NC). 

Method: Resected lung tissue from NSCLC patients (n=35), sub-grouped as COPD current and ex-smokers, patients with small airway (SA) disease and normal lung function smokers compared to NC (n=11), were immuno-stained for EMT biomarkers: E-cadherin, N-cadherin, S100A4, Vimentin, and epidermal growth factor receptor (EGFR). Biomarkers were analysed in the SA epithelium and sub-epithelial layers. Tissue analysis was done with microscope-assisted Image-ProPlus 7.0 software. 

Results: Compared to NC, in all pathological groups, SA wall thickness was significantly increased (p<0.05); SA epithelial E-cadherin expression markedly decreased (p<0.01), whereas N-cadherin, Vimentin, S100A4, and EGFR expression were notably increased (p<0.01). Vimentin expression in sub-epithelium showed a similar trend to epithelium across all pathological groups (p<0.05). However, such changes were only seen in Rbm for S100A4 (p<0.05). EGFR and N-cadherin expressions in both cancer phenotypes were markedly higher than Vimentin and S100A4 (p<0.0001). EMT markers expression positively correlated to smoking history.

Conclusion: EMT is a crucial and active process in NSCLC patients with COPD, resulting in SA remodelling and cancer development. This is the first study to show such changes in broadly phenotyped individuals, suggesting EMT as a key mechanism and novel therapeutic target.