Detection of N‑glycoprotein associated with IgA nephropathy in urine as a potential diagnostic biomarker using glycosylated proteomic analysis

使用糖基化蛋白质组学分析检测尿液中与 IgA 肾病相关的 N 糖蛋白作为潜在的诊断生物标志物

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作者:Junjie Liu, Liuguo Wu, Hongjing Gu, Miaomiao Lu, Jiong Zhang, Hongli Zhou

Abstract

The aim of the present study was to elucidate the potential diagnostic value of urinary N-glycoprotein in patients with IgA nephropathy (IgAN) using mass spectrometry (MS). All procedures were performed between June 2021 and June 2023 at Guangan People's Hospital (Guangan, China). Fresh mid-morning fasting midstream urine samples were collected from a total of 30 patients with IgAN and 30 sex- and age-matched healthy volunteers. Data acquired from 6 participants are available through ProteomeXchange with the identifier PXD041151. By comparison between the IgAN group (n=3) and healthy controls (n=3) and selection criteria of P<0.05 and |log fold-change|>2, a total of 11 upregulated and 22 downregulated glycoproteins in patients with IgAN were identified. The results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggested that glycoproteins are involved in various functions, such as the regulation of cell growth, cell adhesion, cellular component organization and protein binding, as well as multiple pathways, including p53, Notch and mTOR signaling pathways. The urine levels of afamin were further measured by ELISA in a validation cohort to assess the diagnostic performance of the single indicator model. In conclusion, MS-based proteomics of urinary glycoproteins may be an alternative option for diagnosing patients with IgAN. Biomarkers of IgAN may include, but are not limited to, CCL25, PD-L1, HLA-DRB1, IL7RD and WDR82. In addition, the levels of urinary AFM indicators are of diagnostic value for IgAN.

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