Molecular profiling of EGFR family in chronic obstructive pulmonary disease: correlation with airway obstruction

Authors

  • Aristotelis Anagnostis,

    1. Department of Thoracic Medicine, University Hospital of Heraklion, Crete, Greece
    2. Laboratory of Molecular and Cellular Pulmonology, Medical School, University of Crete, Heraklion, Greece
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    • The two authors contributed equally to the work.
  • Eirini Neofytou,

    1. Laboratory of Molecular and Cellular Pulmonology, Medical School, University of Crete, Heraklion, Greece
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    • The two authors contributed equally to the work.
  • Nikolaos Soulitzis,

    1. Laboratory of Molecular and Cellular Pulmonology, Medical School, University of Crete, Heraklion, Greece
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  • Dimitris Kampas,

    1. Laboratory of Molecular and Cellular Pulmonology, Medical School, University of Crete, Heraklion, Greece
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  • Ioannis Drositis,

    1. Department of Thoracic Surgery, University Hospital of Heraklion, Crete, Greece
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  • Despina Dermitzaki,

    1. Department of Anaesthesiology, University Hospital of Heraklion, Crete, Greece
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  • Nikolaos Tzanakis,

    1. Department of Thoracic Medicine, University Hospital of Heraklion, Crete, Greece
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  • Sofia Schiza,

    1. Department of Thoracic Medicine, University Hospital of Heraklion, Crete, Greece
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  • Nikolaos M. Siafakas,

    1. Department of Thoracic Medicine, University Hospital of Heraklion, Crete, Greece
    2. Laboratory of Molecular and Cellular Pulmonology, Medical School, University of Crete, Heraklion, Greece
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  • Eleni G. Tzortzaki

    Corresponding author
    1. Department of Thoracic Medicine, University Hospital of Heraklion, Crete, Greece
    2. Laboratory of Molecular and Cellular Pulmonology, Medical School, University of Crete, Heraklion, Greece
    • Correspondence to: Eleni Tzortzaki, Assistant Professor in Respiratory Medicine, Department of Thoracic Medicine, University Hospital of Heraklion, Medical School, University of Crete, 71003 Heraklion, Crete, Greece. Tel.: (+30) 2810 392433; fax: (+30) 2810 542650; e-mail: tzortzaki@med.uoc.gr

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Abstract

Background

Growth factors mediate various cellular responses to environmental stimuli. Specifically, exposure of lung epithelium to oxidative stress induced by cigarette smoke stimulates aberrant epidermal growth factor receptor (ERBB) family activation. This study's objective was to evaluate the expression of ERBB1–4 receptors in the lung tissue of smokers with or without chronic obstructive pulmonary disease (COPD).

Materials and methods

ERBBs expression was measured by microarray analysis in lung tissue samples from five patients with COPD and five non-COPD smokers, and by quantitative real-time PCR in additional 20 patients with COPD (GOLD stage II), 15 non-COPD smokers and 10 nonsmoker controls.

Results

Microarray data analysis revealed that ERBB receptors expression was elevated in patients with COPD compared to non-COPD smokers, ranging from 1·62- to 2·45-fold, (P < 0·01). Real-time qPCR verified that patients with COPD had higher ERBB1–3 expression levels compared with non-COPD smokers (PERBB1 < 0·001; PERBB2 = 0·003; PERBB3 = 0·003) and nonsmokers (PERBB1 = 0·019; PERBB2 = 0·005; PERBB3 = 0·011). On the other hand, ERBB4 mRNA levels gradually increased from nonsmokers (0·74 ± 0·19) to non-COPD smokers (1·11 ± 0·05) to patients with COPD (1·57 ± 0·28) and were correlated with the degree of airflow obstruction (PFEV1 < 0·001).

Discussion

These data suggest that ERBB1–3 overexpression is not related only to smoking exposure but probably to epithelial remodelling and mucociliary system distortion, characterizing COPD. Additionally, the inverse correlation of ERBB4 with FEV1 exhibits a possible link between ERBB4 and COPD severity.

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