title: Metabolomics provide new insights on lung cancer staging and discrimination from chronic obstructive pulmonary disease.
abstract: Chronic obstructive pulmonary disease (COPD) and lung cancer are widespread lung diseases. Cigarette smoking is a high risk factor for both the diseases. COPD may increase the risk of developing lung cancer. Thus, it is crucial to be able to distinguish between these two pathological states, especially considering the early stages of lung cancer. Novel diagnostic and monitoring tools are required to properly determine lung cancer progression because this information directly impacts the type of the treatment prescribed. In this study, serum samples collected from 22 COPD and 77 lung cancer (TNM stages I, II, III, and IV) patients were analyzed. Then, a collection of NMR metabolic fingerprints was modeled using discriminant orthogonal partial least squares regression (OPLS-DA) and further interpreted by univariate statistics. The constructed discriminant models helped to successfully distinguish between the metabolic fingerprints of COPD and lung cancer patients (AUC training=0.972, AUC test=0.993), COPD and early lung cancer patients (AUC training=1.000, AUC test=1.000), and COPD and advanced lung cancer patients (AUC training=0.983, AUC test=1.000). Decreased acetate, citrate, and methanol levels together with the increased N-acetylated glycoproteins, leucine, lysine, mannose, choline, and lipid (CH3-(CH2)n-) levels were observed in all lung cancer patients compared with the COPD group. The evaluation of lung cancer progression was also successful using OPLS-DA (AUC training=0.811, AUC test=0.904). Based on the results, the following metabolite biomarkers may prove useful in distinguishing lung cancer states: isoleucine, acetoacetate, and creatine as well as the two NMR signals of N-acetylated glycoproteins and glycerol.
authors.affiliation: Faculty of Chemistry, Opole University, Pl. Kopernika 11a, 45-040 Opole, Poland.
authors.forename: Stanislaw
authors.initials: S
authors.lastname: Deja
authors.affiliation: Department and Clinic of Pulmonology and Lung Cancers, Wroclaw Medical University, Grabiszynska 105, 53-439 Wroclaw, Poland.
authors.forename: Irena
authors.initials: I
authors.lastname: Porebska
authors.affiliation: Department and Clinic of Pulmonology and Lung Cancers, Wroclaw Medical University, Grabiszynska 105, 53-439 Wroclaw, Poland.
authors.forename: Aneta
authors.initials: A
authors.lastname: Kowal
authors.affiliation: Department of Bioorganic Chemistry Wrocław University of Technology, Wybrzeze Wyspianskiego 27, 50-370 Wroclaw, Poland.
authors.forename: Adam
authors.initials: A
authors.lastname: Zabek
authors.affiliation: Department of Physiology, Wroclaw Medical University, T. Chalubinskiego 10, 50-368 Wroclaw, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Barg
authors.affiliation: Department and Clinic of Thoracic Surgery, Wroclaw Medical University, Grabiszynska 105, 53-430 Wroclaw, Poland.
authors.forename: Konrad
authors.initials: K
authors.lastname: Pawelczyk
authors.affiliation: Institute of Chemistry, The University of Silesia, Szkolna 9, 40-006 Katowice, Poland.
authors.forename: Ivana
authors.initials: I
authors.lastname: Stanimirova
authors.affiliation: Institute of Chemistry, The University of Silesia, Szkolna 9, 40-006 Katowice, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Daszykowski
authors.affiliation: Department and Clinic of Pulmonology and Lung Cancers, Wroclaw Medical University, Grabiszynska 105, 53-439 Wroclaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Korzeniewska
authors.affiliation: Department and Clinic of Pulmonology and Lung Cancers, Wroclaw Medical University, Grabiszynska 105, 53-439 Wroclaw, Poland.
authors.forename: Renata
authors.initials: R
authors.lastname: Jankowska
authors.affiliation: Department of Bioorganic Chemistry Wrocław University of Technology, Wybrzeze Wyspianskiego 27, 50-370 Wroclaw, Poland. Electronic address: piotr.mlynarz@pwr.wroc.pl.
authors.forename: Piotr
authors.initials: P
authors.lastname: Mlynarz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D003937:Diagnosis, Differential; D016002:Discriminant Analysis; D018450:Disease Progression; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D016018:Least-Squares Analysis; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor
keywords: (1)H NMR spectroscopy; COPD—chronic obstructive pulmonary disease; Lung cancer; Metabolic fingerprinting; Metabolomics