High-resolution mass spectrometry proteomics for the identification of candidate plasma protein biomarkers for chronic obstructive pulmonary disease

Abstract

Although cigarette smoking is recognized as the most important cause of chronic obstructive pulmonary disease (COPD), the pathophysiological mechanisms underlying the lung function decline are not well understood. Using off-line strong cation exchange fractionation with RP-LC-ESI-MS/MS and robust database searching, 1758 tryptic peptides were identified in plasma samples from cigarette smokers. Using two statistical approaches, 30 peptides were identified to be associated with the annualized rate of lung function decline over 5 years among smokers with COPD characterized as having rapid (n = 18) or slow (n = 18) decline and 18 smokers without COPD. The identified peptides belong to proteins that are involved in the complement or coagulation systems or have antiprotease or metabolic functions. This research demonstrates the utility of proteomic profiling to improve the understanding of molecular mechanisms involved in cigarette smoking-related COPD by identifying plasma proteins that correlate with decline in lung function.

Keywords::

• COPD
• cigarette smoking
• biomarker
• mass spectrometry
• protein
• plasma

Acknowledgements

The authors gratefully acknowledge the contributions to this study and manuscript by Michael S. Paul, PhD and Alex Lindell from LineaGen, Inc., Salt Lake City, UT and George J. Patskan, PhD from Altria Client Services. The authors also acknowledge the comments of reviewers Michael Oldham, PhD and Marc R. Kraus, PhD, the editorial assistance of Eileen Y. Ivasauskas of Accuwrit Inc., data management by Zaigang Liu, and sample preparation by Rebecca Secrist. Financial support was provided by Philip Morris USA Inc. and LineaGen, Inc.

Declaration of interest

E.vdO. was a consultant for Altria Client Services. The Center for Biomarker Research and Personalized Medicine was made possible in part by a start-up gift from Philip Morris USA Inc. to the VCU School of Pharmacy. T.B.L., J.S.E., W.K. and J.W.F. are employees of Altria Client Services. E.L.M. and B.K.Z. were employees of Altria Client Services at the time of manuscript preparation. The other authors declare no potential conflicts of interest. The authors alone are responsible for the content and writing of the paper.