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Plasma amino acids and oxylipins as potential multi-biomarkers for predicting diabetic macular edema.

ABSTRACT: To investigate the pathophysiologic characteristics of diabetic complications, we identified differences in plasma metabolites in subjects with type 2 diabetes (T2DM) with or without diabetic macular edema (DME) and a disease duration > 15 years. An cohort of older T2DM patients with prolonged disease duration was established, and clinical information and biospecimens were collected following the guidelines of the National Biobank of Korea. DME phenotypes were identified by ophthalmologic specialists. For metabolomics studies, propensity matched case and control samples were selected. To discover multi-biomarkers in plasma, non-targeted metabolite profiling and oxylipin profiling in the discovery cohort were validated in an extended cohort. From metabolomic studies, 5 amino acids (asparagine, aspartic acid, glutamic acid, cysteine, and lysine), 2 organic compounds (citric acid and uric acid) and 4 oxylipins (12-oxoETE, 15-oxoETE, 9-oxoODE, 20-carboxy leukotriene B4) were identified as candidate multi-biomarkers which can guide DME diagnosis among non-DME subjects. Receiver operating characteristic curves revealed high diagnostic value of the combined 5 amino acids and 2 organic compounds (AUC = 0.918), and of the 4 combined oxylipins (AUC = 0.957). Our study suggests that multi-biomarkers may be useful for predicting DME in older T2DM patients.

SUBMITTER: Rhee SY

PROVIDER: S-EPMC8102569 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Plasma amino acids and oxylipins as potential multi-biomarkers for predicting diabetic macular edema.

Rhee Sang Youl SY Jung Eun Sung ES Suh Dong Ho DH Jeong Su Jin SJ Kim Kiyoung K Chon Suk S Yu Seung-Young SY Woo Jeong-Taek JT Lee Choong Hwan CH

Scientific reports 20210506 1

To investigate the pathophysiologic characteristics of diabetic complications, we identified differences in plasma metabolites in subjects with type 2 diabetes (T2DM) with or without diabetic macular edema (DME) and a disease duration > 15 years. An cohort of older T2DM patients with prolonged disease duration was established, and clinical information and biospecimens were collected following the guidelines of the National Biobank of Korea. DME phenotypes were identified by ophthalmologic specia ...[more]

PMID: 33958610

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Project description:BackgroundCD8+T lymphocytes have a strong pro-inflammatory effect in all parts of the tissue, and some studies have demonstrated that its concentration in the vitreous increased significantly, suggesting that CD8+T cells play a pivotal role in the inflammatory response of diabetic retinopathy (DR). However, the infiltration of CD8+T cells in the DR retina, especially in diabetic macular edema (DME), and its related genes are still unclear.MethodsDownload the GSE16036 dataset from the Gene Expression Omnibus (GEO) database. The ImmuCellAI program was performed to evaluate the abundance of 24 immune cells including CD8+T cells. The CD8+T cell-related genes (DECD8+TRGs) between non-proliferative diabetic retinopathy (NPDR) and DME were detected via difference analysis and correlation analysis. Enrichment analysis and protein-protein interaction (PPI) network mapping were implemented to explore the potential function of DECD8+TRGs. Lasso regression, support vector machine recursive feature elimination (SVM-RFE), CytoHubba plug-in and MCODE plug-in in Cytoscape software, and Weighted Gene Co-Expression Network Analysis (WGCNA) were performed to comprehensively analyze and obtain Hub DECD8+TRGs. Hub DECD8+TRGs expression patterns were further validated in other two DR-related independent datasets. The CD8+TRG score was defined as the genetic characterization of Hub DECD8+TRGs using the GSVA sample scoring method, which can be administered to distinguish early and advanced diabetic nephropathy (DN) as well as normal and DN. Finally, the transcription level of DECD8+TRGs in DR model mouse were verified by quantitative real-time PCR (qPCR).ResultsA total of 371 DECD8+TRGs were identified, of which 294 genes were positively correlated and only 77 genes were negatively correlated. Eight genes (IKZF1, PTPRC, ITGB2, ITGAX, TLR7, LYN, CD74, SPI1) were recognized as Hub DECD8+TRGs. DR and DN, which have strong clinical correlation, have been proved to be associated with CD8+T cell-related hub genes by multiple independent data sets. Hub DECD8+TRGs can not only distinguish PDR from normal and DN from normal, but also play a role in the early and progressive stages of the two diseases (NPDR vs DME, Early DN vs Advanced DN). The qPCR transcription level and trend of Hub DECD8+TRGs in DR mouse model was basically the same as that in human transcriptome.ConclusionThis study not only increases our understanding of the molecular mechanism of CD8+T cells in the progression of DME, but also expands people's cognitive vision of the molecular mechanism of crosstalk of CD8+T cells in the eyes and kidneys of patients with diabetes.

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Plasma amino acids and oxylipins as potential multi-biomarkers for predicting diabetic macular edema.

Publications

Plasma amino acids and oxylipins as potential multi-biomarkers for predicting diabetic macular edema.

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