Development of Diagnostic Biomarkers for Detecting Diabetic Retinopathy at Early Stages Using Quantitative Proteomics.
Development of Diagnostic Biomarkers for Detecting Diabetic Retinopathy at Early Stages Using Quantitative Proteomics.
复制标题
DOI：
10.1155/2016/6571976
复制
发表时间：
2016
影响因子：
4.3
通讯作者：
Kim Y
中科院分区：
文献类型：
--
作者：
Jin J;Min H;Kim SJ;Oh S;Kim K;Yu HG;Park T;Kim Y
糖尿病视网膜病变（DR）是糖尿病（DM）引起的常见微血管并发症，是成年人视力损害和丧失的主要原因。在这里，我们进行了全面的蛋白质组学分析，以发现DR的生物标志物。首先，为了识别在人类玻璃体中特异性表达的生物标志物候选者，我们对先前发表的DR相关研究和我们的实验数据进行了数据挖掘;然后选择了96种蛋白质。为了确认和验证所选择的生物标志物候选物，使用来自无DR的糖尿病患者（无DR）和患有轻度或中度非增殖性糖尿病视网膜病变（Mi或Mo NPDR）的糖尿病患者的血浆，使用半定量多反应监测（SQ-MRM）和稳定同位素稀释多反应监测（SID-MRM）来选择、确认和验证候选物。此外，我们使用在SID-MRM分析中鉴定的15种生物标志物候选物进行了多重测定，这导致合并的AUC值为0.99（无DR相对于Mo NPDR）和0.93（无DR相对于Mi和Mo NPDR）。虽然需要更大样本量的进一步验证，但4蛋白标记物组（APO 4，C7，CLU和ITIH 2）可以代表用于检测DR早期阶段的有用的多生物标志物模型。
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.