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

Abstract

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.

Correlation Study of Peripheral Blood miR-155 and miR-146a Expression Levels with Diabetic Peripheral Neuropathy in Patients with Type 2 Diabetes

“…Additionally, there was no signi cant difference in miR-155 expression levels between the painful and nonpainful neuropathy subgroups. Other clinical studies have reported similar ndings [33] , wherein peripheral blood miR-155 expression was downregulated in patients with T2DM but signi cantly increased in patients with Diabetic Foot Ulcer (DFU), possibly linked to the ongoing in ammatory state in DFU. Chen J et al [34] reported that silencing miR-155 could improve sciatic nerve damage, enhance angiogenesis and alleviate in ammation in DPN rats.…”

Role of Increased miR-222-3p Expression in Peripheral Blood and Wound Marginal Tissues of Type 2 Diabetes Mellitus Patients with Diabetic Foot Ulcer

“…The PB sampling has a low trauma risk, and it is easy and convenient to determine miR-222-3p in PB. On that account, combining our study with previous studies, 20 , 39 we recommend detecting miR-222-3p expression in PB to predict the therapeutic outcome of DFU.…”

“…Ulcer healing after eight weeks referred to spontaneous complete wound closure after eight weeks of DFU treatment (100% re-epithelialization), and recorded 8 weeks after the treatment. 20 …”

“…According to multivariate regression analysis, the diabetes duration, HbA1c, TcPO2, CRP, and hypoalbuminemia could independently affect foot ulcer occurrence, which conformed to previous study results. 20,28 Further, the DFU group presented obviously higher miR-222-3p level in PB and WMT relative to the T2DM group. In the DFU group, the miR-222-3p expression in PB and WMT exhibited a positive relevance to the foot ulcer duration, Wagner grade, and severity of IDSA infection, and a negative relevance to foot ulcer healing rate following eight weeks of treatment.…”

Endogenous Biological Drivers in Diabetic Lower Limb Wounds Recurrence: Hypothetical Reflections

“…A large number of microRNAs have been implicated in pathological diabetic healing [ 50 , 51 , 52 , 53 , 54 , 55 ]. A recent study identified the enhanced expression of miR-155 in the peripheral blood of T2DM patients as a potential predictor for the onset of DFU [ 56 ], whereas the expression level of miR-203 in patients with DFU positively correlated with the severity of the damage [ 57 ]. A high expression level of miR-34c positively correlated with the amputation rates while negatively with the healing response and was also identified as an independent risk factor for ulceration and osteomyelitis [ 58 ].…”