Evaluation of Serum microRNAs in Patients with Diabetic Kidney Disease: A Nested Case-Controlled Study and Bioinformatics Analysis
Evaluation of Serum microRNAs in Patients with Diabetic Kidney Disease: A Nested Case-Controlled Study and Bioinformatics Analysis
复制标题
糖尿病肾病患者血清 microRNA 的评估：巢式病例对照研究和生物信息学分析
DOI：
10.12659/msm.913265
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发表时间：
2019-03-05
影响因子：
3.1
通讯作者：
Chen, LuLu
中科院分区：
文献类型：
--
作者：
Regmi, Anita;Liu, Geng;Chen, LuLu
背景糖尿病肾病（DKD）可导致终末期肾病和肾功能衰竭。本研究旨在检测血清microRNA（miRNAs）、miR-20 a、miR-99 b、miR-122- 5 p和miR-486- 5 p的表达，并利用生物信息学数据研究DKD的相关通路。材料/方法收集25例健康志愿者、50例无并发症的2型糖尿病（T2 DM）患者和42例T2 DM合并DKD患者的血清，检测其miRNA水平。采用实时定量聚合酶链反应（qRT-PCR）检测血清miRNAs的表达。通过分析受试者工作特征（ROC）曲线下面积（AUC）评估DKD患者血清miRNA之间相关性的特异性和敏感性。比较两组患者的血清miRNAs水平和临床指标。生物信息学数据分析获得了参与DKD发病机制相关通路的miRNA靶点。结果与健康对照组相比，DKD组血清miR-99 b和miR-122水平显著升高，miR-20 a和miR-486水平显著降低。血清miR-20 a、miR-99 b、miR-486- 5 p和miR-122- 5 p水平与白蛋白尿、估计肾小球滤过率（eGFR）、血糖和血脂谱显著相关。ROC曲线分析显示，miR-99 b血清水平对DKD的诊断准确性上级miR-486- 5 p、miR-122- 5 p和miR-20 a，AUC分别为0.895、0.853、0.80和0.697。这四种miRNAs调节影响氧化应激、炎症和凋亡的几种基因。结论血清miR-99 b、miR-486- 5 p、miR-122- 5 p和miR-20 a在T2 DM和DKD患者中存在差异表达，应进一步评价其作为DKD潜在生物标志物的价值。
Background Diabetic kidney disease (DKD) can result in end-stage kidney disease and renal failure. This study aimed to examine the expression of serum microRNAs (miRNAs), miR-20a, miR-99b, miR-122-5p, and miR-486-5p, and to use bioinformatics data to investigate the pathways involved in DKD. Material/Methods Serum miRNAs were obtained from 25 healthy volunteers, 50 patients with non-complicated type 2 diabetes mellitus (T2DM), and 42 patients with T2DM and DKD. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of serum miRNAs. Specificity and sensitivity of the association between serum miRNAs in DKD were evaluated by analysis of the receiver operating characteristic (ROC) area under the curve (AUC). Serum miRNAs and clinical parameters of the patients were compared. Bioinformatics data analysis accessed the miRNA targets involved in the pathways related to the pathogenesis of DKD. Results Serum levels of miR-99b and miR-122 significantly increased, and mir-20a and miR-486 decreased in the DKD group compared with healthy controls. Serum levels of miR-20a, miR-99b, miR-486-5p, and miR-122-5p were significantly correlated with albuminuria, estimated glomerular filtration rate (eGFR), blood glucose and lipid profiles. ROC curve analysis showed that diagnostic accuracy of serum levels of miR-99b for DKD was superior to miR-486-5p, miR-122-5p, and miR-20a, resulting in AUCs of 0.895, 0.853, 0.80, and 0.697, respectively. These four miRNAs regulate several genes affecting oxidative stress, inflammation, and apoptosis. Conclusions Serum miR-99b, miR-486-5p, miR-122-5p, and miR-20a were differentially expressed in patients with T2DM and DKD and should be evaluated further as potential biomarkers for DKD.