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Journal of Diabetes Research
Volume 2016, Article ID 6571976, 22 pages
http://dx.doi.org/10.1155/2016/6571976
Research Article

Development of Diagnostic Biomarkers for Detecting Diabetic Retinopathy at Early Stages Using Quantitative Proteomics

1Department of Biomedical Sciences, Seoul National University College of Medicine, 28 Yongon-Dong, Seoul 110-799, Republic of Korea
2Department of Biomedical Engineering, Seoul National University College of Medicine, 28 Yongon-Dong, Seoul 110-799, Republic of Korea
3Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Republic of Korea
4Department of Biostatistics, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, 20 Borame-ro 5-gil, Dongjak-gu, Seoul 156-707, Republic of Korea
5Department of Ophthalmology, Seoul National University College of Medicine, 28 Yongon-Dong, Seoul 110-799, Republic of Korea
6Department of Statistics, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-747, Republic of Korea

Received 10 November 2014; Accepted 5 March 2015

Academic Editor: Ying-Feng Zheng

Copyright © 2016 Jonghwa Jin et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Diabetic retinopathy (DR) is a common microvascular complication caused by diabetes mellitus (DM) and is a leading cause of vision impairment and loss among adults. Here, we performed a comprehensive proteomic analysis to discover biomarkers for DR. First, to identify biomarker candidates that are specifically expressed in human vitreous, we performed data-mining on both previously published DR-related studies and our experimental data; 96 proteins were then selected. To confirm and validate the selected biomarker candidates, candidates were selected, confirmed, and validated using plasma from diabetic patients without DR (No DR) and diabetics with mild or moderate nonproliferative diabetic retinopathy (Mi or Mo NPDR) using semiquantitative multiple reaction monitoring (SQ-MRM) and stable-isotope dilution multiple reaction monitoring (SID-MRM). Additionally, we performed a multiplex assay using 15 biomarker candidates identified in the SID-MRM analysis, which resulted in merged AUC values of 0.99 (No DR versus Mo NPDR) and 0.93 (No DR versus Mi and Mo NPDR). Although further validation with a larger sample size is needed, the 4-protein marker panel (APO4, C7, CLU, and ITIH2) could represent a useful multibiomarker model for detecting the early stages of DR.