Combined with dynamic serum proteomics and clinical follow-up to screen the serum proteins to promote the healing of diabetic foot ulcer

Abstract

Objective Non-healing diabetic foot ulcers are a leading cause of disability and death in diabetic patients, which often results in lower limb amputation. This study aimed to investigate the impact of biomarkers on the healing of diabetic foot ulcers by utilizing dynamic serum proteomics and skin proteomic analysis, combined with clinical case follow-up studies. Methods To analyze dynamic serum proteomic changes in four groups, age-matched normal subjects, diabetic patients, pre-treatment diabetic foot ulcer patients, and healed diabetic foot ulcer patients were selected. The differential proteins were screened in conjunction with normal and diabetic foot ulcer skin proteomics. In this study, a total of 80 patients with diabetic foot ulcers were enrolled and monitored for 3–6 months during treatment. To verify the significance of the differential proteins, age-matched diabetic patients (240 patients) and healthy controls (160 patients) were included as controls. Results Dynamic serum proteomics trend showed that the level of negative regulatory proteins related to endothelial cell migration, angiogenesis, and vascular development was significantly decreased after treatment of diabetic foot ulcer. This study also found that there is an opposite trend of differential protein biological processes, which is mainly enriched in protein activation cascade, immunoglobulin production, and complement activation. The researchers identified the core proteins APOA1, LPA, and APOA2 through a convergence of serum and skin proteomics screening. Clinical cases further validated that APOA1 levels are decreased in diabetic foot ulcer patients and are correlated with disease severity. Conclusions Based on our dynamic proteomics and clinical case studies, our bioinformatic analysis suggests that APOA1 plays a critical role in linking coagulation, inflammation, angiogenesis, and wound repair, making it a key protein that promotes the healing of diabetic foot ulcers.