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
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摘要
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%;PBMC miRNA(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.
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.
引文
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[2] Janoutova J,Janackova P,Sery O,et al.Epidemiology and risk factors of schizophrenia[J].Neuro Endocrinol Lett,2016,37(1):1-8.
[3] Davison J,O' Gorman A,Brennan L,et al.A systematic review of metabolite biomarkers of schizophrenia[J].Schizophr Res,2018,195:32-50.
[4] Li H,Zhang X,Guo Y,et al.A case-control study of genetic association of the PLA2G4A gene with schizophrenia in a Chinese population[J].Psychiatr Genet,2007,17(3):205.
[5] Kapelski P,Skibinska M,Maciukiewicz M,et al.Family-based association study of interleukin 6 (IL6) and its receptor (IL6R) functional polymorphisms in schizophrenia in the Polish population[J].J Neuroimmunol,2015,285:62-67.
[6] Kalia M,Costa ESJ.Biomarkers of psychiatric diseases:current status and future prospects[J].Metabolism,2015,64(3 Suppl 1):S11-15.
[7] Abdul Razak SR,Baba Y,Nakauchi H,et al.DNA methylation is involved in the expression of miR-142-3p in fibroblasts and induced pluripotent stem cells[J].Stem Cells Int,2014:101349.
[8] Xiao C,Rajewsky K.MicroRNA control in the immune system:basic principles[J].Cell,2009,136(1):26-36.
[9] Gilad S,Meiri E,Yogev Y,et al.Serum microRNAs are promising novel biomarkers[J].PLoS One,2008,3(9):e3148.
[10] Chen X,Ba Y,Ma L,et al.Characterization of microRNAs in serum:a novel class of biomarkers for diagnosis of cancer and other diseases[J].Cell Res,2008,18(10):997-1006.
[11] Peng F,Li H,Xiao H,et al.Identification of a three miRNA signature as a novel potential prognostic biomarker in patients with bladder cancer[J].Oncotarget,2017,8(62):105553-105560.
[12] Liu Y,Chang X,Hahn CG,et al.Non-coding RNA dysregulation in the amygdala region of schizophrenia patients contributes to the pathogenesis of the disease[J].Transl Psychiatry,2018,8(1):44.
[13] Gallego J,Alsop E,Lencz T,et al.F10.Differential expression of microRNAs in cerebrospinal fluid and plasma samples in schizophenia[J].Schizophr Bull,2018,44(Suppl 1):S221-222.
[14] Lai CY,Lee SY,Scarr E,et al.Aberrant expression of microRNAs as biomarker for schizophrenia:from acute state to partial remission,and from peripheral blood to cortical tissue[J].Transl Psychiatry,2016,6(1):e717.
[15] Liu S,Zhang F,Shugart YY,et al.The early growth response protein 1-miR-30a-5p-neurogenic differentiation factor 1 axis as a novel biomarker for schizophrenia diagnosis and treatment monitoring[J].Transl Psychiatry,2017,7(1):e998.
[16] Geaghan M,Cairns M.Investigating peripheral microRNA-mRNA interactions in schizophenia[J].Schizophr Bull,2018,44(Suppl 1):S400-401.
[17] Liu S,Zhang F,Wang X,et al.Diagnostic value of blood-derived microRNAs for schizophrenia:results of a meta-analysis and validation[J].Sci Rep,2017,7(1):15328.
[18] Lai CY,Yu SL,Hsien MH,et al.MicroRNA expression aberration as potential peripheral blood biomarkers for schizophrenia[J].PLoS One,2011,6(6):e21635.
[19] Kroh EM,Parkin RK,Mitchell PS,et al.Analysis of circulating microRNA biomarkers in plasma and serum using quantitative reverse transcription-PCR (qRT-PCR)[J].Methods,2010,50(4):298-301.
[20] Burmistrova OA,Goltsov AY,Abramova LI,et al.MicroRNA in schizophrenia:genetic and expression analysis of miR-130b (22q11)[J].Biochemistry (Mosc),2007,72(5):578-582.
[21] Smalheiser NR,Lugli G,Zhang H,et al.Expression of microRNAs and other small RNAs in prefrontal cortex in schizophrenia,bipolar disorder and depressed subjects[J].PLoS One,2014,9(1):e86469.
[22] Wei H,Yuan Y,Liu S,et al.Detection of circulating miRNA levels in schizophrenia[J].American J Psychiatry,2015,172(11):1141-1147.
[23] Walker RM,Rybka J,Anderson SM,et al.Preliminary investigation of miRNA expression in individuals at high familial risk of bipolar disorder[J].J Psychiatr Res,2015,62:48-55.
[24] Sun XY,Zhang J,Niu W,et al.A preliminary analysis of microRNA as potential clinical biomarker for schizophrenia[J].Am J Med Genet B Neuropsychiatr Genet,2015,168(3):170-178.