Application of proteomics in the discovery of candidate protein biomarkers in a diabetes autoantibody standardization program sample subset

作者：Metz Thomas O^*; Qian Wei Jun; Jacobs Jon M; Gritsenko Marina A; Moore Ronald J; Polpitiya Ashoka D; Monroe Matthew E; Camp David G II; Mueller Patricia W; Smith Richard D

来源：Journal of Proteome Research, 2008, 7(2): 698-707.

DOI：10.1021/pr700606w

• diabetes
• proteomics
• Fourier transform ion cyclotron resonance
• label-free quantitation
• liquid chromatography
• mass spectrometry

Novel biomarkers of type 1 diabetes must be identified and validated in initial, exploratory studies before they can be assessed in proficiency evaluations. Currently, untargeted "-omics" approaches are underutilized in profiling studies of clinical samples. This report describes the evaluation of capillary liquid chromatography (LC) coupled with mass spectrometry (MS) in a pilot proteomic analysis of human plasma and serum from a subset of control and type 1 diabetic individuals enrolled in the Diabetes Autoantibody Standardization Program, with the goal of identifying candidate biomarkers of type 1 diabetes. Initial high-resolution capillary LC-MS/MS experiments were performed to augment an existing plasma peptide database, while subsequent LC-FTICR studies identified quantitative differences in the abundance of plasma proteins. Analysis of LC-FTICR proteomic data identified five candidate protein biomarkers of type 1 diabetes. alpha-2-Glycoprotein 1 (zinc), corticosteroid-binding globulin, and lumican were 2-fold up-regulated in type 1 diabetic samples relative to control samples, whereas clusterin and serotrahsferrin were 2-fold up-regulated in control samples relative to type 1 diabetic samples. Observed perturbations in the levels of all five proteins are consistent with the metabolic aberrations found in type 1 diabetes. While the discovery of these candidate protein biomarkers of type 1 diabetes is encouraging, follow up studies are required for validation in a larger population of individuals and for determination of laboratory-defined sensitivity and specificity values using blinded samples.

• 出版日期2008-2