Multiplatform Metabolomics Reveals Novel Serum Metabolite Biomarkers in Diabetic Retinopathy Subjects,Advanced Science

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Multiplatform Metabolomics Reveals Novel Serum Metabolite Biomarkers in Diabetic Retinopathy Subjects
Advanced Science ( IF 14.3 ) Pub Date : 2020-10-01 , DOI: 10.1002/advs.202001714
Qiuhui Xuan _{1,

2} , Yang Ouyang _{1,

2} , Yanfeng Wang _{1,

2} , Liang Wu ₃ , Huating Li ₃ , Yuanyuan Luo _{1,

2} , Xinjie Zhao ₁ , Disheng Feng _{1,

2} , Wangshu Qin ₁ , Chunxiu Hu ₁ , Lina Zhou ₁ , Xinyu Liu ₁ , Haidong Zou ₄ , Chun Cai ₃ , Jiarui Wu _{5,

6} , Weiping Jia _{3,

7} , Guowang Xu _{1,

2,

8}

Affiliation

CAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical Physics Chinese Academy of Sciences 457 Zhongshan Road Dalian 116023 China.
University of Chinese Academy of Sciences Beijing 100049 China.
Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Metabolic diseases biobank Shanghai JiaoTong University Affiliated Sixth People's Hospital Shanghai 200233 China.
Department of Ophthalmology First People's Hospital of Shanghai Shanghai Jiao Tong University Shanghai China.
Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences Chinese Academy of Sciences 320 Yue-Yang Road Shanghai 200031 China.
Key Laboratory of Systems Biology CAS Center for Excellence in Molecular Cell Science Institute of Biochemistry and Cell Biology University of Chinese Academy of Sciences Chinese Academy of Sciences 320 Yue-Yang Road Shanghai 200031 China.
Shanghai Diabetes Institute Shanghai Key Laboratory of Diabetes Mellitus Shanghai Clinical Center for Endocrine and Metabolic Diseases Shanghai Jiaotong University Affiliated Sixth People's Hospital Shanghai 200233 China.
CAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical Physics Chinese Academy of Sciences Dalian 116023 China.

Diabetic retinopathy (DR) is the main cause of vision loss or blindness in working age adults worldwide. The lack of effective diagnostic biomarkers for DR leads to unsatisfactory curative treatments. To define potential metabolite biomarkers for DR diagnosis, a multiplatform‐based metabolomics study is performed. In this study, a total of 905 subjects with diabetes without DR (NDR) and with DR at different clinical stages are recruited. Multiplatform metabolomics methods are used to characterize the serum metabolic profiles and to screen and validate the DR biomarkers. Based on the criteria p < 0.05 and false‐discovery rate < 0.05, 348 and 290 metabolites are significantly associated with the pathogenesis of DR and early‐stage DR, respectively. The biomarker panel consisting of 12‐hydroxyeicosatetraenoic acid (12‐HETE) and 2‐piperidone exhibited better diagnostic performance than hemoglobin A1c (HbA1c) in differentiating DR from diabetes, with AUCs of 0.946 versus 0.691 and 0.928 versus 0.648 in the discovery and validation sets, respectively. In addition, this panel showed higher sensitivity in early‐stage DR detection than HbA1c. In conclusion, this multiplatform‐based metabolomics study comprehensively revealed the metabolic dysregulation associated with DR onset and progression. The defined biomarker panel can be used for detection of DR and early‐stage DR.

中文翻译：

多平台代谢组学揭示了糖尿病视网膜病变受试者的新型血清代谢生物标志物

糖尿病视网膜病变 (DR) 是全世界工作年龄成年人视力丧失或失明的主要原因。缺乏有效的 DR 诊断生物标志物导致治疗效果不令人满意。为了定义用于 DR 诊断的潜在代谢生物标志物，进行了基于多平台的代谢组学研究。在这项研究中，总共招募了 905 名患有不同临床阶段的 DR 的糖尿病受试者（NDR）和患有 DR 的受试者。多平台代谢组学方法用于表征血清代谢谱并筛选和验证 DR 生物标志物。根据p < 0.05 和错误发现率 < 0.05 的标准，348 种和 290 种代谢物分别与 DR 和早期 DR 的发病机制显着相关。由 12-羟基二十碳四烯酸 (12-HETE) 和 2-哌啶酮组成的生物标志物组在区分 DR 和糖尿病方面表现出比糖化血红蛋白 (HbA1c) 更好的诊断性能，在发现和验证集中 AUC 分别为 0.946 与 0.691 以及 0.928 与 0.648 ，分别。此外，该面板在早期 DR 检测中表现出比 HbA1c 更高的灵敏度。总之，这项基于多平台的代谢组学研究全面揭示了与 DR 发病和进展相关的代谢失调。确定的生物标志物组可用于检测 DR 和早期 DR。

更新日期：2020-11-19

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