title: Quantitative mass spectrometry analysis using PAcIFIC for the identification of plasma diagnostic biomarkers for abdominal aortic aneurysm.
abstract: BACKGROUND
  Abdominal aortic aneurysm (AAA) is characterized by increased aortic vessel wall diameter (>1.5 times normal) and loss of parallelism. This disease is responsible for 1-4% mortality occurring on rupture in males older than 65 years. Due to its asymptomatic nature, proteomic techniques were used to search for diagnostic biomarkers that might allow surgical intervention under nonlife threatening conditions.
  
  
  RESULTS
  Pooled human plasma samples of 17 AAA and 17 control patients were depleted of the most abundant proteins and compared using a data-independent shotgun proteomic strategy, Precursor Acquisition Independent From Ion Count (PAcIFIC), combined with spectral counting and isobaric tandem mass tags. Both quantitative methods collectively identified 80 proteins as statistically differentially abundant between AAA and control patients. Among differentially abundant proteins, a subgroup of 19 was selected according to Gene Ontology classification and implication in AAA for verification by Western blot (WB) in the same 34 individual plasma samples that comprised the pools. From the 19 proteins, 12 were detected by WB. Five of them were verified to be differentially up-regulated in individual plasma of AAA patients: adiponectin, extracellular superoxide dismutase, protein AMBP, kallistatin and carboxypeptidase B2.
  
  
  CONCLUSIONS
  Plasma depletion of high abundance proteins combined with quantitative PAcIFIC analysis offered an efficient and sensitive tool for the screening of new potential biomarkers of AAA. However, WB analysis to verify the 19 PAcIFIC identified proteins of interest proved inconclusive save for five proteins. We discuss these five in terms of their potential relevance as biological markers for use in AAA screening of population at risk.
authors.affiliation: INSERM, U744, Lille, France.
authors.forename: Adelina E
authors.initials: AE
authors.lastname: Acosta-Martin
authors.forename: Alexandre
authors.initials: A
authors.lastname: Panchaud
authors.forename: Maggy
authors.initials: M
authors.lastname: Chwastyniak
authors.forename: Annabelle
authors.initials: A
authors.lastname: Dupont
authors.forename: Francis
authors.initials: F
authors.lastname: Juthier
authors.forename: Corinne
authors.initials: C
authors.lastname: Gautier
authors.forename: Brigitte
authors.initials: B
authors.lastname: Jude
authors.forename: Philippe
authors.initials: P
authors.lastname: Amouyel
authors.forename: David R
authors.initials: DR
authors.lastname: Goodlett
authors.forename: Florence
authors.initials: F
authors.lastname: Pinet
mesh_terms: D000368:Aged; D017544:Aortic Aneurysm, Abdominal / Q000097:blood* / Q000378:metabolism; D015415:Biomarkers / Q000097:blood*; D015153:Blotting, Western; D005260:Female; D006801:Humans; D007610:Kallikreins / Q000737:chemistry; D007705:Kinins / Q000737:chemistry; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D008875:Middle Aged; D010455:Peptides / Q000737:chemistry; D020543:Proteome; D040901:Proteomics / Q000379:methods; D012984:Software
chemical_list: D015415:Biomarkers; D007705:Kinins; D010455:Peptides; D020543:Proteome; D007610:Kallikreins