Application of proteomics in the discovery of candidate protein biomarkers in a diabetes autoantibody standardization program sample subset.
Title | Application of proteomics in the discovery of candidate protein biomarkers in a diabetes autoantibody standardization program sample subset. |
Publication Type | Journal Article |
Year of Publication | 2008 |
Authors | Metz TO, Qian W-J, Jacobs JM, Gritsenko MA, Moore RJ, Polpitiya AD, Monroe ME, Camp DG, Mueller PW, Smith RD |
Journal | J Proteome Res |
Keywords | Autoantibodies, Biological Markers, Carrier Proteins, Chondroitin Sulfate Proteoglycans, Chromatography, Liquid, Diabetes Mellitus, Type 1, Follow-Up Studies, Glycoproteins, Humans, Keratan Sulfate, Proteomics, Tandem Mass Spectrometry, Transcortin |
Abstract | 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 serotransferrin 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. |
DOI | 10.1021/pr700606w |
Alternate Journal | J. Proteome Res. |
PubMed ID | 18092746 |
PubMed Central ID | PMC2672959 |
Grant List | 106-310 / / PHS HHS / United States 106-554 / / PHS HHS / United States 107-360 / / PHS HHS / United States DK070146 / DK / NIDDK NIH HHS / United States P41 RR018522-05 / RR / NCRR NIH HHS / United States PL105-33 / / PHS HHS / United States R33 DK070146-03 / DK / NIDDK NIH HHS / United States RR18522 / RR / NCRR NIH HHS / United States |