Increased Expression of miR-155 in Peripheral Blood and Wound Margin Tissue of Type 2 Diabetes Mellitus Patients Associated with Diabetic Foot Ulcer

Diabetes Metab Syndr Obes. 2022 Nov 3:15:3415-3428. doi: 10.2147/DMSO.S376292. eCollection 2022.

Abstract

Purpose: To investigate the correlations of miR-155 expression in the peripheral blood and wound margin tissue of patients with diabetic foot ulcer (DFU) and explore the clinical value of miR-155 as a potential biomarker for the diagnosis and treatment outcomes of DFU.

Methods: Sixty newly diagnosed T2DM patients without DFU (T2DM group), 112 T2DM patients with DFU (DFU group), and 60 healthy controls (NC group) were included. MiR-155 levels in the peripheral blood and wound margin tissue were determined by quantitative real-time PCR, while clinical features and risk factors of DFU were explored. Multiple stepwise logistic regression analysis was used to determine whether miR-155 expression was an independent risk factor for DFU. The diagnostic effectiveness of miR-155 level on DFU was evaluated using ROC curve analysis.

Results: A significant decrease in the expression level of miR-155 was observed in T2DM group compared with NC group (P < 0.05), while a markedly increased miR-155 expression level was noted in DFU group compared with T2DM group (P < 0.01). Moreover, there was a negative correlation between the expression levels of miR-155 with healing rate of DFU. Kaplan-Meier survival curve analysis showed that the cumulative rate of unhealed DFU in miR-155 high expression group is higher than that in miR-155 low expression group, both in peripheral blood and wound margin tissue (log rank, P = 0.004, P < 0.001, respectively). The multivariate logistic regression analysis confirmed that a high expression of miR-155 was an independent risk factor for DFU. The ROC curve analysis indicated that the AUC of miR-155 for the diagnosis of DFU was 0.794, with the optimum sensitivity being 96.82% and the optimum specificity of 95.93%.

Conclusion: The increased expression of miR-155 in peripheral blood of T2DM patients is closely related to the occurrence of DFU. MiR-155 is a potentially valuable biomarker for diagnosis and prognosis of DFU.

Keywords: biomarker; diabetic foot ulcer; miR-155; microRNAs; type 2 diabetes mellitus.

Grants and funding

This study was supported by the Natural Science Foundation of Anhui Province in China (2108085MH269) and the Natural Science Research Project of Colleges and Universities in Anhui Province (KJ2021A0274). The funding body had no role in the design of the study, or the collection, analysis, and interpretation of data, or in writing the manuscript.