Abstract

Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) commonly coexist in smokers, and the presence of COPD increases the risk of developing LC. Cigarette smoke causes oxidative stress and an inflammatory response in lung cells, which in turn may be involved in COPD and lung cancer development. The aim of this study was to identify differential proteomic profiles related to oxidative stress response that were potentially involved in these two pathological entities. Protein content was assessed in the bronchoalveolar lavage (BAL) of 60 patients classified in four groups: COPD, COPD and LC, LC, and control (neither COPD nor LC). Proteins were separated into spots by two dimensional polyacrylamide gel electrophoresis (2D-PAGE) and examined by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/TOF). A total of 16 oxidative stress regulatory proteins were differentially expressed in BAL samples from LC and/or COPD patients as compared with the control group. A distinct proteomic reactive oxygen species (ROS) protein signature emerged that characterized lung cancer and COPD. In conclusion, our findings highlight the role of the oxidative stress response proteins in the pathogenic pathways of both diseases, and provide new candidate biomarkers and predictive tools for LC and COPD diagnosis.

Highlights

  • Cigarette smoking has been recognized as the most important causative factor of chronic obstructive pulmonary disease (COPD) and it is associated with more than 90% of lung cancer cases [1]

  • The experiments were performed in bronchoalveolar lavage (BAL) samples extracted from a cohort of 60 patients divided into four groups whose characteristics are described in Average age

  • We presented a 2D-PAGE proteomic evaluation of BAL fluid in patients with the two most relevant smoking related diseases, lung cancer and COPD

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Summary

Introduction

Cigarette smoking has been recognized as the most important causative factor of COPD and it is associated with more than 90% of lung cancer cases [1]. Lung cancer accounts for 12% of all cancer diagnoses worldwide, making it the largest cause of cancer-associated death worldwide, accounting for more than one million casualties per year worldwide. COPD is a major independent risk factor for lung carcinoma, among long-term smokers. The presence of COPD increases the risk of lung cancer up to 4.5-fold. 50%–70% of patients diagnosed with lung cancer have spirometric evidence of COPD [2]. Inhaled oxidants from smoke generate cellular damage by directly targeting proteins, lipids, and nucleic acids, and deplete the level of antioxidants in the lung, thereby overwhelming the oxidant/antioxidant balance of the lung, leading to increased oxidative stress [4]

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