Journal of Capital Medical University

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To explore the potential biomarkers of proliferative diabetic retinopathy by plasma proteomics

Yang Fangyuan1,2, Peng Shijie3, Liu Jing4, Yang Jinkui1,2, Zhu Xiaorong1*    

  1. 1. Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730,China; 2. Beijing Diabetes Institute, Beijing 100730, China; 3. Department of Endocrinology, Beijing Geriatric Hospital, Beijing 100089, China; 4. Department of Infectious Disease, Beijing Haidian Hospital, Beijing 100080, China
  • Received:2024-03-04
  • Supported by:
    This study was supported by National Natural Science Foundation of China (81561128015, 81930019),National Key R&D Program of China(2017YFC0909600), Beijing Municipal Administration of Hospitals Incubating Program (PX2020008)

Abstract: Objective  To identify potential biomarkers of proliferative diabetic retinopathy (PDR) through the difference of protein expression between PDR patients and diabetes patients without retina diseases (NDR) by using isobaric tag for relative and absolute quantification (iTRAQ) proteomics. Methods  A total of 42 patients admitted to the Department of Endocrinology, Beijing Tongren Hospital from 2016 to 2017 were recruited, including 21 PDR patients and 21 gender- and age-matched NDR patients. After proteins extraction from patients' serum samples, iTRAQ labeling with liquid chromatograph-mass spectrometer and mass spectrometer (LC-MS/MS) analysis was performed to screen the differential proteins. Gene Ontology (GO)enrichment and Kyoto Encyclopedia of Genes and Genome(KEGG) pathway were analyzed. Comparisons were conducted using independent sample t-tests, to determine the changes in protein expression levels through fold change (FC) and P-values. Results  Totally 29 differentially expressed proteins were identified based on a FC>1.2 (up/down) and a P value ≤ 0.05. Among them, 8 proteins were upregulated and 21 proteins were downregulated in the PDR group. GO enrichment analysis showed that the functions of differentially expressed genes were classified into three categories: biological processes, cellular components, and molecular functions. The differential gene expressions were involved in biological regulation, cell composition, cellular metabolic processes, and cell binding or catalytic activity. KEGG pathway analysis showed that the most significantly upregulated angiotensin converting enzyme (ACE) is involved in the renin angiotensin system (RAS) and renin secretion pathways. The upregulated protein insulin like growth factor I (IGF-1) is involved in metabolic related signaling pathways, including HIF-1, FoxO, mTOR, PI3K-Akt, and AMPK. The significantly downregulated protein myosin-6 is involved in myocardial cell contraction and signaling pathways. Conclusion  The iTRAQ proteomics analysis suggested, many differential expressed proteins between PDR and NDR groups. ACE, IGF-1 and myosin-6 were potential serum diagnostic markers and maybe new therapeutic targets for diabetic retinopathy.

Key words: diabetic retinopathy, serum proteomics, biomarkers, liquid phase mass spectrometry

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