Department of Neurochemistry, National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru 560029, Karnataka, India.
Department of Neurology, National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru 560029, Karnataka, India.
Age Ageing. 2017 Sep 1;46(5):861-864. doi: 10.1093/ageing/afx090.
the diagnosis of cerebral small vessel disease, a leading cause of vascular dementia (VaD), relies solely on neuroimaging studies. Circulating microRNAs (miRNAs) have been proposed as diagnostic biomarkers in various disorders. Our aim was to identify differentially expressed, circulating miRNAs in small vessel VaD which could serve as diagnostic biomarkers for this disease.
we performed plasma miRNA profiling by quantitative polymerase chain reaction (qPCR) array in small vessel VaD patients and age- and gender-matched, cognitively normal and healthy controls. Selected, differentially expressed miRNAs were validated by qPCR. Sensitivity, specificity and area under the curve (AUC) were calculated for each individual miRNA.
profiling results showed that 44 miRNAs were differentially expressed in small vessel VaD cases (P < 0.05 with a fold change of <2 or >2). A set of seven, highly differentially expressed miRNAs (fold change of <3.6 or >3.6), were estimated in a cohort of 204 small vessel VaD patients and 200 healthy, age and gender-matched controls. Validation study revealed that four miRNAs (miR-409-3p, miR-502-3p, miR-486-5p and miR-451a) could be used as valuable biomarkers for identifying the disease. Sensitivity, specificity and AUC for these miRNAs were 76, 75, 75 and 70%; 89, 89, 83 and 75% and 0.94, 0.92, 0.90 and 0.86, respectively. However, combined receiver operating characteristic curve analysis of seven miRNAs revealed an AUC of 0.64 with sensitivity of 55.5% and specificity of 65.7%.
plasma miR-409-3p, miR-502-3p, miR-486-5p and miR-451a could be used to differentiate small vessel VaD patients from healthy controls. Large-scale studies of their biomarker potential are warranted.
脑小血管病是血管性痴呆（VaD）的主要病因，其诊断仅依赖于神经影像学研究。循环 microRNAs（miRNAs）已被提出作为各种疾病的诊断生物标志物。我们的目的是鉴定小血管 VaD 中差异表达的、可作为该疾病诊断生物标志物的循环 miRNAs。
我们通过定量聚合酶链反应（qPCR）阵列对小血管 VaD 患者及年龄和性别匹配的认知正常和健康对照者的血浆 miRNA 进行了谱分析。通过 qPCR 验证了选定的差异表达 miRNA。计算了每个 miRNA 的灵敏度、特异性和曲线下面积（AUC）。
分析结果显示，在小血管 VaD 病例中，有 44 个 miRNA 表达差异（P < 0.05，倍数变化<2 或>2）。在 204 例小血管 VaD 患者和 200 例年龄和性别匹配的健康对照者的队列中，估计了一组 7 个高度差异表达的 miRNAs（倍数变化<3.6 或>3.6）。验证研究表明，4 个 miRNA（miR-409-3p、miR-502-3p、miR-486-5p 和 miR-451a）可作为识别该疾病的有价值的生物标志物。这些 miRNA 的灵敏度、特异性和 AUC 分别为 76%、75%、75%和 70%；89%、89%、83%和 75%以及 0.94、0.92、0.90 和 0.86。然而，7 个 miRNA 的联合受试者工作特征曲线分析显示 AUC 为 0.64，灵敏度为 55.5%，特异性为 65.7%。
血浆 miR-409-3p、miR-502-3p、miR-486-5p 和 miR-451a 可用于区分小血管 VaD 患者和健康对照者。需要进一步研究其作为生物标志物的潜力。
