Epithelial-mesenchymal transition (EMT) changes in non-small cell lung cancer patients with early COPD

Background EMT might be central to lung cancer development in smokers and COPD. We illustrate EMT changes in a broader demographic of patient groups who were diagnosed with non-small cell lung cancer (adenocarcinoma and squamous cell carcinoma). These included COPD current and ex-smokers, patients with small airway (SA) disease and normal lung function smokers compared to normal controls (NC). Methods We had access to surgically resected SA tissue from 46 subjects and assessed for airway wall thickness and immunohistochemically for EMT biomarkers: E-cadherin, N-cadherin, S100A4, Vimentin, and epidermal growth factor receptor (EGFR). All tissue analysis was done with a computer and microscope-assisted Image-pro Plus 7.0 software. Results Airway wall thickness significantly increased across all pathological groups (p<0.05) compared to NC. SA epithelial E-cadherin expression markedly decreased (p<0.01), and increase in N-cadherin, Vimentin, S100A4, and EGFR expression was observed in all pathological groups compared to NC (p<0.01). Vimentin-positive cells in reticular basement membrane (Rbm), lamina propria (LP), and adventitia showed a similar trend to epithelium across all pathological groups (p<0.05); however, such changes were only observed in Rbm for S100A4 (p<0.05). Vimentin was higher in adenocarcinoma versus squamous cell carcinoma; in contrast, S100A4 was higher in the squamous cell carcinoma group. EGFR and N-cadherin expressions in both phenotypes were markedly higher than E-cadherin, Vimentin and S100A4 (p<0.0001). Conclusion EMT is an active process in the SA of smokers and COPD diagnosed with non-small cell lung cancer, contributing to small airway remodelling and cancer development as seen in these patients.