Journal
JOURNAL OF PROTEOME RESEARCH
Volume 7, Issue 2, Pages 698-707Publisher
AMER CHEMICAL SOC
DOI: 10.1021/pr700606w
Keywords
diabetes; proteomics; Fourier transform ion cyclotron resonance; label-free quantitation; liquid chromatography; mass spectrometry
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Funding
- NCRR NIH HHS [RR18522, P41 RR018522-05, P41 RR018522] Funding Source: Medline
- NIDDK NIH HHS [R21 DK070146, R33 DK070146-03, PL105-33, DK070146, R33 DK070146] Funding Source: Medline
- PHS HHS [106-554, 107-360, 106-310] Funding Source: Medline
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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.
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