Label-Free Liquid Chromatography–Mass Spectrometry Proteomic Analysis of Urinary Identification in Diabetic Vascular Dementia in a Han Chinese Population

摘要

Objective: This study aimed to identify potential diagnostic biomarkers of diabetic vascular dementia (DVD) and unravel the underlying mechanisms using mass spectrometry (MS). Methods: Label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomic analysis was applied to urine samples from four groups, including 14 patients with vascular dementia (VD), 22 patients with type 2 diabetes mellitus (T2DM), 12 patients with DVD, and 21 normal controls (NCs). Searching the MS data by Proteome Discoverer software (ThermoFisher Scientific; Waltham, MA, USA), protein abundances were analyzed qualitatively and quantitatively and compared between these groups. Combining bioinformatics analysis using Gene Ontology (GO), pathway crosstalk analysis using Kyoto Encyclopedia of Genes and Genomes (KEGG), protein–protein interaction (PPI) network analysis using STRING, and literature searching, the differentially expressed proteins (DEPs) of DVD can be comprehensively judged and were further quantified by receiver operating characteristic (ROC) curve methods. Results: The proteomic findings showed quantitative changes in patients with DVD compared to patients with NC, T2DM, and VD groups; among 4,744 identified urine proteins, 1,222, 1,152, and 1,180 proteins displayed quantitative changes unique to DVD vs. NC, T2DM, and VD, respectively, including 481 overlapped common DEPs. Then, nine unique proteins [including HP, SERPIND, ATP5PB, VNN2, ALDH3A1, U2AF2, C6, A0A5C2GRG5 (no name), and A0A5C2FZ29 (no name)] and two composite markers (CM) (A0A5C2GRG5+U2AF2 and U2AF2+C6) were confirmed by a ROC curve method. Conclusion: This study provided an insight into the potential pathogenesis of DVD and elucidated a method for early detection.