Analytical and Bioanalytical Chemistry

, Volume 397, Issue 5, pp 1809–1819 | Cite as

Proteomic biomarkers in plasma that differentiate rapid and slow decline in lung function in adult cigarette smokers with chronic obstructive pulmonary disease (COPD)

  • Gaurav S. J. B. Rana
  • Timothy P. York
  • Jeffery S. Edmiston
  • Barbara K. Zedler
  • Joel G. Pounds
  • Joshua N. Adkins
  • Richard D. Smith
  • Zaigang Liu
  • Guoya Li
  • Bradley T. Webb
  • Edward L. Murrelle
  • Jason W. Flora
Original Paper

Abstract

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of morbidity and mortality in the United States and cigarette smoking is a primary determinant of the disease. COPD is characterized by chronic airflow limitation as measured by the forced expiratory volume in one second (FEV1). In this study, the plasma proteomes of 38 middle-aged or older adult smokers with mild to moderate COPD, with FEV1 decline characterized as either rapid (RPD, n = 20) or slow or absent (SLW, n = 18), were interrogated using a comprehensive high-throughput proteomic approach, the accurate mass and time (AMT) tag technology. This technology is based upon a putative mass and time tag database (PMT), high-resolution LC separations and high mass accuracy measurements using FT-ICR MS with a 9.4-T magnetic field. The peptide and protein data were analyzed using three statistical approaches to address ambiguities related to the high proportion of missing data inherent to proteomic analysis. The RPD and SLW groups were differentiated by 55 peptides which mapped to 33 unique proteins. Twelve of the proteins have known roles in the complement or coagulation cascade and, despite an inability to adjust for some factors known to affect lung function decline, suggest potential mechanistic biomarkers associated with the rate of lung function decline in COPD. Whether these proteins are the cause or result of accelerated decline will require further research.

Keywords

Amino acids/peptides Bioanalytical methods Biological samples Clinical/biomedical analysis Genomics/proteomics 

Abbreviations

AMT

accurate mass and time

COPD

chronic obstructive pulmonary disease

FEV1

forced expiratory volume in one second

FVC

forced vital capacity

GAP

Genetics of Addiction Project

LHS

Lung Health Study

NHLBI

National Heart, Lung, and Blood Institute

PMT

putative mass and time

RPD

FEV1 rapid decliner group

SLW

FEV1 slow decliner group

Xcorr

cross-correlation score

Notes

Acknowledgments

The authors gratefully acknowledge the contributions to this study and manuscript by Michael S. Paul, Ph.D. and Alex Lindell from LineaGen, Inc., Salt Lake City, Utah and George J. Patskan, Ph.D. from Altria Client Services. The authors also acknowledge the comments of reviewers Rutger Van der Hoeven, Ph.D. and Marc R. Kraus, Ph.D. and the editorial assistance of Eileen Ivasauskas of Accuwrit Inc. Financial support was provided by Philip Morris USA Inc. and LineaGen, Inc.

Conflicts of interest

The authors of this manuscript have no financial/commercial conflicts of interest.

Supplementary material

216_2010_3742_MOESM1_ESM.xls (4 mb)
ESM 1A total of 3,549 non-redundant peptides were identified from 80 independent MS runs (two technical replicates per sample), representing 533 proteins. A collection of all peptides, abundances (log-transformed), and related proteins can be found in the following Excel Table (XLS 4039 kb)

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Gaurav S. J. B. Rana
    • 1
  • Timothy P. York
    • 2
  • Jeffery S. Edmiston
    • 1
  • Barbara K. Zedler
    • 1
  • Joel G. Pounds
    • 3
  • Joshua N. Adkins
    • 3
  • Richard D. Smith
    • 3
  • Zaigang Liu
    • 1
  • Guoya Li
    • 1
  • Bradley T. Webb
    • 2
  • Edward L. Murrelle
    • 1
  • Jason W. Flora
    • 1
  1. 1.Health Sciences, Altria Client Services, Research Development & EngineeringRichmondUSA
  2. 2.Departments of Human and Molecular Genetics and Pharmacy, Institute for Biomarker Discovery and Personalized MedicineVirginia Commonwealth University School of MedicineRichmondUSA
  3. 3.Biological Sciences DivisionPacific Northwest National LaboratoryRichlandUSA

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