title: Development of Diagnostic Biomarkers for Detecting Diabetic Retinopathy at Early Stages Using Quantitative Proteomics.
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.
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, 28 Yongon-Dong, Seoul 110-799, Republic of Korea ; Department of Biomedical Engineering, Seoul National University College of Medicine, 28 Yongon-Dong, Seoul 110-799, Republic of Korea.
authors.forename: Jonghwa
authors.initials: J
authors.lastname: Jin
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, 28 Yongon-Dong, Seoul 110-799, Republic of Korea.
authors.forename: Hophil
authors.initials: H
authors.lastname: Min
authors.affiliation: Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Republic of Korea.
authors.forename: Sang Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Biostatistics, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, 20 Borame-ro 5-gil, Dongjak-gu, Seoul 156-707, Republic of Korea.
authors.forename: Sohee
authors.initials: S
authors.lastname: Oh
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, 28 Yongon-Dong, Seoul 110-799, Republic of Korea ; Department of Biomedical Engineering, Seoul National University College of Medicine, 28 Yongon-Dong, Seoul 110-799, Republic of Korea.
authors.forename: Kyunggon
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Ophthalmology, Seoul National University College of Medicine, 28 Yongon-Dong, Seoul 110-799, Republic of Korea.
authors.forename: Hyeong Gon
authors.initials: HG
authors.lastname: Yu
authors.affiliation: Department of Statistics, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 151-747, Republic of Korea.
authors.forename: Taesung
authors.initials: T
authors.lastname: Park
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, 28 Yongon-Dong, Seoul 110-799, Republic of Korea ; Department of Biomedical Engineering, Seoul National University College of Medicine, 28 Yongon-Dong, Seoul 110-799, Republic of Korea.
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Kim
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D057225:Data Mining; D003930:Diabetic Retinopathy / Q000175:diagnosis* / Q000378:metabolism; D042241:Early Diagnosis; D006801:Humans; D013058:Mass Spectrometry; D040901:Proteomics / Q000379:methods*
chemical_list: D015415:Biomarkers