血浆及外周血单个核细胞微小RNA在精神分裂症诊断中的研究

Research on microRNAs in plasma and peripheral blood mononuclear cell in the diagnosis of schizophrenia

目的:探索血浆及外周血单个核细胞(PBMC)中微小RNA(miRNA)在精神分裂症(SZ)诊断中的价值。方法:根据文献报道筛选出与SZ相关的7种miRNA(has-miR-449a,has-miR-34a-5p,has-miR-652-3p,has-miR-564,has-miR-432-5p,has-miR-548d-5p和has-miR-572);提取35例初诊的SZ患者(患者组)及15名健康体检者(对照组)的抗凝全血的血浆及PBMC中的RNA,采用实时逆转录聚合酶链式扩增反应技术测定血浆及PBMC中这7种miRNA水平,计算其相对表达量。结果:患者组血浆及PBMC中4种miRNA(miR-652-3p,miR-564,miR-432-5p和miR-548d-5p)相对表达量较对照组明显增加(P均<0.05);患者组7种miRNA的相对表达量血浆明显高于PBMC(P均<0.05);多变量ROC曲线显示,患者组血浆miRNA(has-miR-652-3p,has-miR-564,has-miR-548d-5p)ROC曲线下面积为98%,灵敏度为90.9%,特异度为95.4%;PBMCmiRNA(has-miR-652-3p,has-miR-564,has-miR-432-5p以及has-miR-548d-5p)ROC曲线下面积为86%;灵敏度为88.2%,特异度为78.3%。结论:SZ患者血浆及PBMC中的miRNA(miR-652-3p,miR-564,miR-432-5p和miR-548d-5p)相对表达量明显增高;血浆miRNA更有潜力成为SZ的分子诊断标志物。

Objective: To explore the diagnostic value of microRNA(miRNA) in plasma and peripheral blood mononuclear cells(PBMC) in schizophrenia(SZ). Method:7 miRNAs(has-miR-449 a,has-miR-34 a-5 p,has-miR-652-3 p,has-miR-564,has-miR-432-5 p,has-miR-548 d-5 p and has-miR-572) were selected according to literatures.RNAs from plasma and PBMC were extracted from 35 newly diagnosed SZ patients(patient group) and 15 healthy subjects(control group).The relative expression levels of these 7 miRNAs in both plasma and PBMC were determined by real-time reverse transcription polymerase chain reaction(RT-PCR). Results:Four of the seven miRNAs(miR-652-3 p,miR-564,miR-432-5 p and miR-548 d-5 p) from both plasma and PBMC in patient group were up-regulated(all P<0.05).The relative expression levels of 7 miRNAs in plasma were significantly higher than those in PBMC(all P<0.05).Multivariate ROC curve analysis showed that, in the patient group,the area under the ROC curve of miRNA(has-miR-652-3 p,has-miR-564,has-miR-548 d-5 p) in plasma was 98%,the sensitivity was 90.9%,and the specificity was 95.4%;the area under the ROC curve of miRNA(has-miR-652-3 p,has-miR-564,has-miR-432-5 p and has-miR-548 d-5 p) in PBMC was 86%,the sensitivity and specificity were 88.2% and 78.3% respectively. Conclusion:The relative expression levels of miRNAs(miR-652-3 p,miR-564,miR-432-5 p and miR-548 d-5 p) in plasma and PBMC of SZ patients are significantly increased.Compared with miRNA in PBMC,miRNA in plasma has more potential to be a molecular diagnostic marker for SZ.