Cathepsin B as a potential serum biomarker for early diagnosis and progression of diabetic foot ulcer complicated with peripheral vascular disease

The existing diagnostic methods of diabetic foot ulcer (DFU) complicated with peripheral vascular disease (PVD) lack sufficient potential for early identification, which leads to slow wound healing, amputation and even death. Thus, this study aimed to explore the potential serum biomarkers of DFU complicated with PVD. A target gene of DFU complicated with PVD was identified using single-cell transcriptome analysis. The immunohistochemistry, ELISA, clinical correlation analysis, tubulogenesis assay, CCK8 assay, and scratch assay were used to verify the correlation between this target gene and DFU complicated with PVD. The ELISA experiment was used to detect the target gene in serum. In this study, the result of PPI in single-cell transcriptomes showed that cathepsin B (CTSB) was enriched in vascular endothelial cells of DFU. The immunohistochemistry and ELISA results revealed that CTSB was highly expressed in the tissues and serum of patients with the combination of DFU and PVD, and this expression increased with the increase of the Wagner grade of DFU. Clinical correlation analysis indicated that CTSB expression is positively correlated with the clinical indicators of the combination of DFU and PVD. Knockdown of CTSB promoted tubulogenesis, proliferation and migration of vascular endothelial cells and overexpression of CTSB has the opposite effect. CTSB, a secretory protein, can be detected as a diagnostic biomarker in serum. Therefore, this study suggested that CTSB can be used as a potential serum diagnostic biomarker for DFU complicated with PVD, which is helpful for the early diagnosis of this disease, prognosis monitoring and adjustment of treatment plans.