High-resolution mass spectrometry proteomics for the identification of candidate plasma protein biomarkers for chronic obstructive pulmonary disease.
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.
York
Timothy P
TP
Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23298-0003, USA. tpyork@vcu.edu
van den Oord
Edwin J C G
EJ
Langston
Timothy B
TB
Edmiston
Jeffery S
JS
McKinney
Willie
W
Webb
Bradley Todd
BT
Murrelle
E Lenn
EL
Zedler
Barbara K
BK
Flora
Jason W
JW
D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000737:chemistry; D001798:Blood Proteins / Q000032:analysis* / Q000737:chemistry; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D010455:Peptides / Q000097:blood / Q000737:chemistry; D020543:Proteome / Q000737:chemistry; D040901:Proteomics; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology; D012907:Smoking / Q000097:blood / Q000453:epidemiology
D015415:Biomarkers; D001798:Blood Proteins; D010455:Peptides; D020543:Proteome