Proteomics and pitfalls in the search for potential biomarkers of abdominal aortic aneurysms.
Proteomics is evolving as an important research technique in cardiovascular disease. We present exploratory research for a systemic biomarker of abdominal aortic aneurysm (AAA) in serum. Forty patients, 20 with large AAAs and 20 matched controls, were prospectively recruited. Serum was harvested, enriched, and mined for differential protein expression. Difference in gel electrophoresis using a two-dimensional platform, cyanine labeling, and Progenesis SameSpots software identified protein spots with significantly altered intensity. Liquid chromatography mass spectrometry aligned to the Seaquest protein database characterized proteins of interest, and 436 protein spots were demonstrated from the 20 processed gels. Thirteen spots of interest, demonstrating fold change (1.7-4) between the two patient cohorts and consistent significant differential expression (analysis of variance, p </= .003), were picked for identification. Four of 13 spots were identified according to their tandem mass spectra. These were fragments of serum albumin, hemoglobin, and apolipoprotein C-II precursor. Identified spots represented proteins highly abundant in serum, not candidate biomarkers. Issues of variability surrounding serum harvest, processing, enrichment, and the challenge of identifying minimally expressed proteins currently limit this avenue of research. No proteins identified in this study had the biologic plausibility to represent a possible biomarker of aneurysmal disease. The tissue proteome may be a more rewarding approach for preliminary investigation of plausible biomarkers.
Nordon
Ian M
IM
St. George's Vascular Institute, St. George's Hospital, Blackshaw Road, London, UK. inordon@sgul.ac.uk
Brar
Ranjeet
R
Hinchliffe
Robert J
RJ
Cockerill
Gillian
G
Thompson
Matthew M
MM
D000368:Aged; D017544:Aortic Aneurysm, Abdominal / Q000097:blood / Q000175:diagnosis*; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000032:analysis*; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D030562:Databases, Protein; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D008131:London; D008297:Male; D011237:Predictive Value of Tests; D011446:Prospective Studies; D040901:Proteomics / Q000379:methods; D053719:Tandem Mass Spectrometry
D015415:Biomarkers; D001798:Blood Proteins