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

Abstract

Ruyan Jie,* Jing Qian,* Ying Tang,* Yutong Li, Murong Xu, Xiaotong Zhao, Mingwei Chen Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaotong Zhao; Mingwei Chen, Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, Anhui, 230032, People’s Republic of China, Tel [phone], Fax [phone], Email [email protected]; [email protected]: To study the correlations of miR-222-3p expression in the peripheral blood and wound marginal tissues of type 2 diabetes mellitus (T2DM) patients with the onset of diabetic foot ulcer (DFU), as well as explore the clinical value possessed by miR-222-3p in the diagnosis and treatment outcomes of DFU.Methods: The study included 70 T2DM patients who did not suffer foot ulcers (T2DM group), 146 T2DM patients who suffered foot ulcers (DFU group), as well as 70 normal controls (NC group). Quantitative real-time PCR determined the MiR-222-3p relative expression. Clinical features and risk factors regarding DFU were assessed. Multiple stepwise logistic regression analysis assisted in confirming whether miR-222-3p expression could serve for independently predicting the risk factors for DFU. ROC curve analysis evaluated the diagnostic value exhibited by miR-222-3p level against DFU.Results: T2DM group exhibited an obviously higher MiR-222-3p expression relative to NC group [1.98 (0.98, 3.62) vs 0.92 (0.61, 1.87)] (P < 0.01), but DFU group exhibited an obviously higher miR-222-3p expression relative to T2DM group [5.61 (1.98, 10.24) vs 1.98 (0.98, 3.62)] (P < 0.01). Besides, miR-222-3p expression presented a negative correlation with DFU healing rate (P < 0.05). According to Kaplan–Meier survival curve analysis, the group with high miR-222-3p expression showed higher unhealed DFU cumulative rate relative to the group with low expression (log-rank, P = 0.011, 0.001, respectively). Multivariate logistic regression analysis confirmed that high miR-222-3p expressions could independently predict DFU risk (OR=3.85, 95% CI 1.18~12.37, P = 0.008). According to the ROC curve analysis, the AUC of miR-222-3p specific to DFU diagnosis reached 0.803, with the best sensitivity of 95.93% and best specificity of 96.27%.Conclusion: The increased expression of miR-222-3p in the peripheral blood of T2DM patients is closely related to the occurrence of DFU. MiR-222-3p is a biomarker with potential clinical value in diagnosing and evaluating the prognosis of DFU.Keywords: miR-222-3p, diabetic foot ulcer, type 2 diabetes mellitus, microRNA, biomarker

Keywords

• mir-222-3p
• diabetic foot ulcer
• type 2 diabetes mellitus
• microrna
• biomarker