Two Novel MicroRNA Biomarkers Related to β-Cell Damage and Their Potential Values for Early Diagnosis of Type 1 Diabetes
Two Novel MicroRNA Biomarkers Related to β-Cell Damage and Their Potential Values for Early Diagnosis of Type 1 Diabetes
复制标题
两种与β细胞损伤相关的新型microRNA生物标志物及其对1型糖尿病早期诊断的潜在价值
DOI：
10.1210/jc.2017-01417
复制
发表时间：
2018-04-01
影响因子：
5.8
通讯作者：
Weng, Jianping
中科院分区：
文献类型：
--
作者：
Liu, Li;Yan, Jinhua;Weng, Jianping
背景：在1型糖尿病（T1DM）进展过程中，需要新的策略和生物标志物来早期检测β细胞损伤。目的：探讨血清microRNAs （miRNA）是否可以作为T1DM的生物标志物。设计、设置和患者：在发现阶段用miRNA微阵列建立miRNA谱（6名T1DM患者，6名对照组）。在训练数据集（40例T1DM， 56例对照）中使用逻辑回归分析建立了基于mirna的T1DM诊断模型，然后使用留一交叉验证和另一个独立验证数据集（33例T1DM， 29例对照）进行验证。主要观察指标：应用定量逆转录聚合酶链反应确认候选mirna在T1DM和对照组之间的差异。采用受试者工作特征曲线下面积（AUC）评价诊断准确性。INS-1细胞、链脲佐菌素处理小鼠（n = 4）和非肥胖糖尿病（NOD）小鼠（n = 12）被用来评估mirna与β细胞损伤的关系。结果：基于发现阶段鉴定的6个候选差异表达mirna，在训练数据集中建立了基于AmiRNA的T1DM诊断准确率较高的模型（AUC = 0.817）。验证数据集显示，该模型具有良好的诊断性能（AUC = 0.804）。miR-1225-5p和miR-320c的分泌在链球菌对佐佐菌素处理的小鼠和INS-1细胞中显著增加。值得注意的是，在NOD小鼠糖尿病进展过程中，这两种mirna的升高是在葡萄糖升高之前观察到的。结论：在新近发病的T1DM患者中发现了与b细胞损伤相关的两种RNA生物标志物（miR-1225-5p和miR-320c）。本研究建立的基于mirna的模型在T1DM的诊断中表现出良好的性能。
Context: New strategies and biomarkers are needed in the early detection of beta-cell damage in the progress of type 1 diabetes mellitus (T1DM).Objective: To explore whether serum microRNAs (miRNA) should be served as biomarkers for T1DM.Design, Settings, and Patients: The miRNA profile was established with miRNA microarray in discovery phase (six T1DM, six controls). A miRNA-basedmodel for T1DM diagnosis was developed using logistic regression analysis in the training dataset (40 T1DM, 56 controls) and then validated with leave-one-out cross validation and another independent validation dataset (33 T1DM, 29 controls).Main Outcome Measures: Quantitative reverse transcription polymerase chain reaction was applied to confirm the differences of candidate miRNAs between T1DM and controls. Area under the receiver-operating characteristic (ROC) curve (AUC) was used to evaluate diagnostic accuracy. INS-1 cells, streptozotocin-treated mice (n = 4), and nonobese diabetic (NOD) mice (n = 12) were used to evaluate the association of miRNAs with beta-cell damage.Results: AmiRNA -based model was established in the training dataset with high diagnostic accuracy for T1DM (AUC = 0.817) based on six candidate differential expressed miRNAs identified in discovery phase. The validation dataset showed the model's satisfactory diagnostic performance (AUC = 0.804). Secretions of miR-1225-5p and miR-320c were significantly increased in strep to zotocin-treated mice and INS-1 cells. Noteworthy, the elevation of these two miRNAs was observed before glucose elevation in the progress of diabetes in NOD mice.Conclusions: Twomi RNA biomarkers (miR-1225-5p and miR-320c) related to b-cell damage were identified in patients with recent-onset T1DM. The miRNA-based model established in this study exhibited a good performance in diagnosis of T1DM.