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Epithelial mesenchymal transition (EMT) and non-small cell lung cancer (NSCLC): a mutual association with airway disease

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Abstract

NSCLC is a leading cause of morbidity and mortality worldwide. It includes adeno- and squamous cell carcinoma. In the background, COPD and smoking play a vital role in development of NSCLC. Local progression and metastasis of NSCLC has been associated with various mechanisms, but in particular by a process called epithelial mesenchymal transition (EMT), which is implicated in COPD pathogenesis. In this study, we have investigated whether expression of EGFR (activation marker) and S100A4, vimentin and N-cadherin (as EMT) is different both in central and leading edge of NSCLC and to what extent related to EMT activity of both small and large airways, stage and differentiation of NSCLC. We have investigated EMT biomarkers (S100A4, vimentin, and N-cadherin), an epithelial activation marker (EGFR) and a vascularity marker (Type-IV collagen) in surgically resected tissue from patients with NSCLC (adeno- and squamous cell carcinoma), and compared them with expression in the corresponding non-tumorous airways. EGFR, S100A4, vimentin, N-cadherin expression was higher in tumor cells located at the peripheral leading edge of NSCLC when compared with centrally located tumor cells of same subjects (P < 0.01). Type-IV collagen-expressing blood vessels were also more at the leading edge in comparison with central parts of NSCLC. EGFR and S100A4 expression was related to differentiation status (P < 0.05) and TNM stage (P < 0.05) of NSCLC. Moreover, EMT markers in the leading edge were significantly related to airway EMT activity, while peripheral edge vascularity of squamous cell carcinoma only was significantly related to large airway Rbm vascularity (P < 0.05). EGFR- and EMT-related protein expression was markedly high in the peripheral leading edge of NSCLCs and related to tumor characteristics associated with poor prognosis. The relationships between EMT-related tumor biomarker expression and those in the airway epithelium and Rbm provide a background for utility of airway changes in clinical settings.

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Abbreviations

CI:

Confidence interval

EMT:

Epithelial mesenchymal transition

EGFR:

Epidermal growth factor receptor

IRS:

Immunoreactive score

NSCLC:

Non-small cell lung cancer

Rbm:

Reticular basement membrane

TNM:

Tumor, node, metastasis

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Acknowledgements

This research was supported by National Health and Medical Research Council (NHMRC) Grant 1001062. The sponsors had no role in the study design; in the collection, analysis, and interpretation of the data; or in the decision to submit the article for publication.

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Authors and Affiliations

  1. NHMRC Centre for Research Excellence in Chronic Respiratory Disease and Lung Ageing, School of Medicine, University of Tasmania, MS1, 17 Liverpool Street, Private Bag 23, Hobart, TAS, 7000, Australia

    Malik Quasir Mahmood, Hans Konrad Muller, Sukhwinder Singh Sohal & Eugene Haydn Walters

  2. Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, Tyne and Wear, UK

    Chris Ward

  3. Faculty of Health, School of Health Sciences, University of Tasmania, Launceston, TAS, 7248, Australia

    Sukhwinder Singh Sohal

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  1. Malik Quasir Mahmood
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  2. Chris Ward
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Correspondence to Eugene Haydn Walters.

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Ethical approval

The Tasmanian health and medical Human Research Ethics Committee approved this study (#EC00337). Informed consent was obtained from all individual participants included in the study. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Mahmood, M.Q., Ward, C., Muller, H.K. et al. Epithelial mesenchymal transition (EMT) and non-small cell lung cancer (NSCLC): a mutual association with airway disease. Med Oncol 34, 45 (2017). https://doi.org/10.1007/s12032-017-0900-y

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