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

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:

• miR-155
• diabetic foot ulcer
• type 2 diabetes mellitus
• microRNAs
• biomarker

Abbreviations

T2DM, type 2 diabetes mellitus; DFU, diabetic foot ulcer; AUC, area under the curves; FPG, fasting plasma glucose; HbA1c, glycosylated hemoglobin A1c; TCH, total cholesterol; TG, triacylglycerol; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; ALB, serum albumin; Hb, hemoglobin; WBC, white blood cell; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; TcPO2, transcutaneous oxygen pressure; ABI, ankle brachial index; qRT-PCR, quantitative real-time PCR assays.

Data Sharing Statement

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Inquiries for data access may be sent to the following e-mail address: [email protected].

Ethical Approval

This study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Anhui Medical University, and we obtained the informed consent of the subjects. All procedures were performed in studies involving human participants in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Acknowledgments

We are grateful to all patients for participating in the study. We thank the participants of this study including the doctors, nurses, and researchers from the Department of Endocrinology and the Burns Department in the First Affiliated Hospital of Anhui Medical University.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

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.