Metabolomic analysis of lung cancer patients with chronic obstructive pulmonary disease using gas chromatography-mass spectrometry

Chronic obstructive pulmonary disease (COPD), characterized by intermittent exacerbations and clinical subphenotypes like emphysema and chronic bronchitis, poses a significant risk of lung cancer (LC) development. Metabolomic studies of COPD are scarce, and those of LC patients with COPD subphenotypes have not been investigated. To study metabolite profile alteration in LC patients with different COPD subphenotypes, lung paracancer tissue from 10 LC (CON) patients, 10 LC patients with emphysema (E), and 9 LC patients with chronic bronchitis (CB) were analyzed using gas chromatography-mass spectrometry. Multivariate analysis indicated a distinct separation between LC patients with COPD subphenotypes and LC patients. Overall, 60, 55, 33 and 63 differential metabolites (DM) were identified in comparisons between CB vs CON, E vs CON, CB vs E, and CB + E vs CON, respectively, and of these, 8 DM were shared in all comparisons. Among the high altered metabolites, E samples showed higher 'acetol' than CON samples, and lower 'azelaic acid', '3-methylglutaric acid' and 'allose'. CB samples showed higher 'turanose' and 'o-phosphoserine' and lower 'anandamide' than CON and E samples. In CB and E samples, 'galactonic acid', '2-mercaptoethanesulfonic acid', 'D-alanyl-D-alanine' '3-methylglutaric acid', 'glycine', 'L-4-Hydroxyphenylglycine' and 'O-phosphonothreonine' had common alteration trends compared with those of CON samples. 'Glycine', 'L-4-Hydroxyphenylglycine' and 'O-phosphonothreonine' were significantly enriched in glycine, serine and threonine metabolism pathways. The total differential metabolites detected were remarkably altered in pyrimidine, beta-alanine and purine metabolism. Our study provided altered DM patterns of lung paracancer tissue, the key metabolites and their enriched metabolic pathways in LC patients with different COPD subphenotypes.