Serum microRNA-221 as a biomarker for diabetic retinopathy in patients associated with type 2 diabetes

Abstract

Aim: To investigate the candidate microRNA (miRNA), miR-221 as a novel biomarker for diabetic retinopathy (DR) in patients associated with type 2 diabetes (T2D).

Methods: The subjects involved were divided into four groups: healthy control (HC), no diabetic retinopathy (NDR), non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) group. Serum miR-221 was validated by real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Also, serum angiotensin II (Ang II) and vascular endothelial growth factor (VEGF) were examined by enzyme-linked immunosorbent assay. In addition, receiver operating characteristic (ROC) curve was performed to explore the diagnostic accuracy of miR-221, Ang II and VEGF for DR in patients with T2D. Spearman's rank correlation coefficient was executed to estimate the correlations of serum miR-221 with metabolic parameters and serum markers in patients with T2D.

Results: Primarily, serum miR-221, Ang II and VEGF were increased significantly in T2D patients compared to HC participant respectively, and progressive up-regulated in NDR, NPDR and PDR groups (P<0.001). Additionally, miR-221 in serum was remarkably positively correlated with metabolic parameters such as glycated hemoglobin (r=0.310, P=0.002) and homeostasis model assessment for insulin resistance (r=0.413, P<0.001), as well as serum markers for instance Ang II (r=0.667, P<0.001) and VEGF (r=0.499, P<0.001). Furthermore, serum miR-221 (AUC, 0.894; 95%CI, 0.833-0.955; P<0.001), Ang II (AUC, 0.888; 95%CI, 0.828-0.949; P<0.001) and VEGF (AUC, 0.785; 95%CI, 0.695-0.875; P<0.001) had evidently diagnostic efficiency in DR, and miR-221 is the most effective among them.

Conclusion: Serum miR-221 as a potential biomarker could be related to not only occurrence but also progression for DR in patients with T2D. However, a prospective clinical trial is warranted.

Keywords: biomarker; diabetic retinopathy; microRNA-221; type 2 diabetes.

Figure 1. Relative expression of serum miR-221 in HC, NDR, NPDR and PDR groups

^aP<0.05 versus HC group; ^bP<0.05 versus NDR group; ^cP<0.05 versus NPDR group.

Figure 2. Expression of serum Ang II and VEGF in HC, NDR, NPDR and PDR groups

^aP<0.05 versus HC group; ^bP<0.05 versus NDR group; ^cP<0.05 versus NPDR group.

Figure 3. Correlation of serum miR-221 with metabolic parameters including HbA1c and HOMA-IR, as well as serum markers involving Ang II and VEGF in patients with T2D.

Figure 4. ROC curves of miR-221, Ang II and VEGF for DR in patients with T2D.