title: Large-scale, ion-current-based proteomics investigation of bronchoalveolar lavage fluid in chronic obstructive pulmonary disease patients.
abstract: Proteomic analysis of bronchoalveolar lavage fluid (BALF) in chronic obstructive pulmonary disease (COPD) patients may provide new biomarkers and deeper understanding of the disease mechanisms but remains challenging. Here we describe an ion-current-based strategy for comparative analysis of BALF proteomes from patients with moderate and stable COPD versus healthy controls. The strategy includes an efficient preparation procedure providing quantitative recovery and a nano-LC/MS analysis with a long, heated column. Under optimized conditions, high efficiency and reproducibility were achieved for each step, enabling a "20-plex" comparison of clinical subjects (n = 10/group). Without depletion/fractionation, a total of 423 unique protein groups were quantified under stringent criteria with at least two quantifiable peptides. Seventy-six proteins were determined as significantly altered in COPD, which represent a diversity of biological processes such as alcohol metabolic process, gluconeogenesis/glycolysis, inflammatory response, proteolysis, and oxidation reduction. Interestingly, altered alcohol metabolism responding to oxidant stress is a novel observation in COPD. The prominently elevated key enzymes involved in alcohol metabolism (e.g., ADH1B, ALDH2, and ALDH3A1) may provide a reasonable explanation for a bewildering observation in COPD patients known for decades: the underestimation of the blood alcohol concentrations through breath tests. These discoveries could provide new insights for identifying novel biomarkers and pathological mediators in clinical studies.
authors.affiliation: Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY 14260 USA.|New York State Center of Excellence in Bioinformatics and Life Sciences, 701 Ellicott Street, Buffalo, NY 14203 USA.
authors.forename: Chengjian
authors.initials: C
authors.lastname: Tu
authors.affiliation: University at Buffalo, SUNY.
authors.forename: Manoj Jacob
authors.initials: MJ
authors.lastname: Mammen
authors.affiliation: Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY 14260 USA.|New York State Center of Excellence in Bioinformatics and Life Sciences, 701 Ellicott Street, Buffalo, NY 14203 USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY 14260 USA.|New York State Center of Excellence in Bioinformatics and Life Sciences, 701 Ellicott Street, Buffalo, NY 14203 USA.
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Shen
authors.affiliation: Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY 14260 USA.|New York State Center of Excellence in Bioinformatics and Life Sciences, 701 Ellicott Street, Buffalo, NY 14203 USA.
authors.forename: Xiaosheng
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY14203.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY14203.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Wang
authors.affiliation: University at Buffalo, SUNY.|WNY VA Healthcare System, NY 14203 USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Sethi
authors.affiliation: Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY 14260 USA.|New York State Center of Excellence in Bioinformatics and Life Sciences, 701 Ellicott Street, Buffalo, NY 14203 USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Qu
mesh_terms: D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid; D001999:Bronchoscopy; D016022:Case-Control Studies; D056148:Chromatography, Reverse-Phase; D006801:Humans; D013058:Mass Spectrometry; D040901:Proteomics; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*