Exploratory Research on the Urine Proteome in Patients With Diabetic Peripheral Neuropathy

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes and there are currently no biomarkers for DPN in clinical practice. The objective of this study was to explore the diagnostic value of urine for diseases and discover potential markers. Urinary proteomics was used to analyze urine samples from patients with DPN and healthy individuals. Quantitative analysis of mass spectrometry data was performed using both group-based and paired individual analysis strategies. A total of 2611 proteins were identified, of which 1759 were quantifiable, and 312 proteins showed significant differences (fold change > 2, adjusted <i>p</i> value < 0.01), with 239 decreased and 73 increased. A random grouping cross-validation strategy was employed to evaluate the differentially expressed proteins, ensuring that the probability of random differences was less than 10%. Unsupervised clustering analysis of urinary proteomes among groups could distinguish most specimens. The most enriched GO biological processes were cytoplasmic translation, translation, exocytosis, chaperone-mediated protein folding and immunoglobulin-mediated immune response. The most significant KEGG signaling pathways were ribosome, coronavirus disease (COVID-19), and metabolic pathways. Furthermore, some differentially expressed proteins were linked to the pathogenesis of diabetes, whereas others were associated with nerve damage. These molecules could serve as potential diagnostic and therapeutic biomarkers; some differential proteins have not yet been reported to be associated with DPN, providing clues for further research on their functions.