Endoplasmic reticulum stress in bronchial tissue in patients with COPD and lung cancer

Abstract

COPD is a risk factor for lung cancer (LC). The mechanisms for this association are unknown. Both diseases can associate disturbances in endoplasmic reticulum stress (ERS).

Hypothesis: ERS could be a mechanism for LC in COPD patients.

Aims: To compare different ERS markers in non-tumour bronchial tissue in smoking patients with/without COPD (with /without LC) and healthy non-smoking controls.

Population and methods: Forty subjects distributed into 4 groups according to the presence or not of COPD and LC. Clinical history, lung function tests and bronchoscopy with bronchial biopsy were performed in all subjects. The most representative markers for ERS (BIP, IRE, xBPS, PERK, CHOP, EIF, ATF6) were analysed by RT-PCR.The values were normalised according to the GADPH.

Results: Smoking subjects with normal lung function without LC, n=7 (5 men, 57 ± 15 years, FEV1 95±14% , FEV1/FVC 78 ± 8%);COPD patients without LC, n=13 (10 men, 66 ± 9 years, FEV1 88 ± 11%, FEV1/FVC 62 ± 6%);Smoking subjects with normal lung function with LC, n=5 (4 men, 58 ± 6 years FEV1 95±12 %, FEV1/FVC 76 ± 3%); COPD patients with LC, n=15 (12 men, 64 ± 11 years, FEV1 72±15 %, FEV1/FVC 60 ± 6%). We found more cellular cycles to detect IRE, PERK and CHOP in patients with COPD and LC compared with those smoking subjects with normal lung function (p<0.01): IRE 1.25 [1.16-1.31] vs 1.08 [1.06-1.18]; PERK 1.20 [1.17-1.26] vs 1.1 [0.99-1.16]; CHOP 1.12 [1.07-1.22] vs 0.95 [0.91-1.05], suggesting that patients with COPD and LC had lower concentrations of these markers.

Conclusions: The patients with COPD and LC show a decreased ERS in bronchial tissue.

Funded partially by FIS PI 12/02793, Grups Competitius MAR Govern Balear 2011-2013.