Multiplatform Metabolomics Reveals Novel Serum Metabolite Biomarkers in Diabetic Retinopathy Subjects

Abstract 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 metabolo...

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Main Authors: Qiuhui Xuan, Yang Ouyang, Yanfeng Wang, Liang Wu, Huating Li, Yuanyuan Luo, Xinjie Zhao, Disheng Feng, Wangshu Qin, Chunxiu Hu, Lina Zhou, Xinyu Liu, Haidong Zou, Chun Cai, Jiarui Wu, Weiping Jia, Guowang Xu
Format: Article
Language:English
Published: Wiley 2020-11-01
Series:Advanced Science
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Online Access:https://doi.org/10.1002/advs.202001714
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author Qiuhui Xuan
Yang Ouyang
Yanfeng Wang
Liang Wu
Huating Li
Yuanyuan Luo
Xinjie Zhao
Disheng Feng
Wangshu Qin
Chunxiu Hu
Lina Zhou
Xinyu Liu
Haidong Zou
Chun Cai
Jiarui Wu
Weiping Jia
Guowang Xu
author_facet Qiuhui Xuan
Yang Ouyang
Yanfeng Wang
Liang Wu
Huating Li
Yuanyuan Luo
Xinjie Zhao
Disheng Feng
Wangshu Qin
Chunxiu Hu
Lina Zhou
Xinyu Liu
Haidong Zou
Chun Cai
Jiarui Wu
Weiping Jia
Guowang Xu
author_sort Qiuhui Xuan
collection DOAJ
description Abstract 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.
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spelling doaj.art-74c2d698dfaf434bbdc267844ffd20152022-12-21T22:05:18ZengWileyAdvanced Science2198-38442020-11-01722n/an/a10.1002/advs.202001714Multiplatform Metabolomics Reveals Novel Serum Metabolite Biomarkers in Diabetic Retinopathy SubjectsQiuhui Xuan0Yang Ouyang1Yanfeng Wang2Liang Wu3Huating Li4Yuanyuan Luo5Xinjie Zhao6Disheng Feng7Wangshu Qin8Chunxiu Hu9Lina Zhou10Xinyu Liu11Haidong Zou12Chun Cai13Jiarui Wu14Weiping Jia15Guowang Xu16CAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical Physics Chinese Academy of Sciences 457 Zhongshan Road Dalian 116023 ChinaCAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical Physics Chinese Academy of Sciences 457 Zhongshan Road Dalian 116023 ChinaCAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical Physics Chinese Academy of Sciences 457 Zhongshan Road Dalian 116023 ChinaShanghai 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 ChinaShanghai 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 ChinaCAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical Physics Chinese Academy of Sciences 457 Zhongshan Road Dalian 116023 ChinaCAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical Physics Chinese Academy of Sciences 457 Zhongshan Road Dalian 116023 ChinaCAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical Physics Chinese Academy of Sciences 457 Zhongshan Road Dalian 116023 ChinaCAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical Physics Chinese Academy of Sciences 457 Zhongshan Road Dalian 116023 ChinaCAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical Physics Chinese Academy of Sciences 457 Zhongshan Road Dalian 116023 ChinaCAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical Physics Chinese Academy of Sciences 457 Zhongshan Road Dalian 116023 ChinaCAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical Physics Chinese Academy of Sciences 457 Zhongshan Road Dalian 116023 ChinaDepartment of Ophthalmology First People's Hospital of Shanghai Shanghai Jiao Tong University Shanghai ChinaShanghai 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 ChinaKey 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 ChinaShanghai 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 ChinaCAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical Physics Chinese Academy of Sciences 457 Zhongshan Road Dalian 116023 ChinaAbstract 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.https://doi.org/10.1002/advs.202001714diabetic retinopathylipidomicsmetabolomicsmultiplatformsserum biomarkers
spellingShingle Qiuhui Xuan
Yang Ouyang
Yanfeng Wang
Liang Wu
Huating Li
Yuanyuan Luo
Xinjie Zhao
Disheng Feng
Wangshu Qin
Chunxiu Hu
Lina Zhou
Xinyu Liu
Haidong Zou
Chun Cai
Jiarui Wu
Weiping Jia
Guowang Xu
Multiplatform Metabolomics Reveals Novel Serum Metabolite Biomarkers in Diabetic Retinopathy Subjects
Advanced Science
diabetic retinopathy
lipidomics
metabolomics
multiplatforms
serum biomarkers
title Multiplatform Metabolomics Reveals Novel Serum Metabolite Biomarkers in Diabetic Retinopathy Subjects
title_full Multiplatform Metabolomics Reveals Novel Serum Metabolite Biomarkers in Diabetic Retinopathy Subjects
title_fullStr Multiplatform Metabolomics Reveals Novel Serum Metabolite Biomarkers in Diabetic Retinopathy Subjects
title_full_unstemmed Multiplatform Metabolomics Reveals Novel Serum Metabolite Biomarkers in Diabetic Retinopathy Subjects
title_short Multiplatform Metabolomics Reveals Novel Serum Metabolite Biomarkers in Diabetic Retinopathy Subjects
title_sort multiplatform metabolomics reveals novel serum metabolite biomarkers in diabetic retinopathy subjects
topic diabetic retinopathy
lipidomics
metabolomics
multiplatforms
serum biomarkers
url https://doi.org/10.1002/advs.202001714
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