精神分裂症疾病诊断标志物circRNAs筛选及验证  

Screening and validation of circRNAs as diagnostic markers for schizophrenia

作　　者：袁洋 楚璐萌 魏雨菲 刘雪玲 曾凌星 张红星 于海川[3] YUAN Yang;CHU Lumeng;WEI Yufei;LIU Xueling;ZENG Lingxing;ZHANG Hongxing;YU Haichuan(School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, Henan 453003,China)

机构地区：[1]新乡医学院医学检验学院,新乡453003 [2]新乡医学院心理学院 [3]新乡医学院第二附属医院,河南省生物精神病学重点实验室

出　　处：《中国神经精神疾病杂志》2019年第5期299-304,共6页Chinese Journal of Nervous and Mental Diseases

基　　金：河南省科技攻关计划项目(编号:172102310583);河南省自然科学基金面上项目(编号:162300410226);新乡医学院精神神经医学学科群开放研究课题(编号:2016PN-KFKT-08);新乡医学院产学研合作项目(编号:2017CXY-2-14);河南省生物精神病学重点实验室开放课题(编号:ZDSYS2016001)

摘　　要：目的研究精神分裂症(schizophrenia,SCZ)患者外周血单个核细胞中环状RNAs(circular RNAs,circRNAs)的差异表达,寻找潜在的SCZ诊断标志物。方法纳入175例SCZ患者和200名对照。将其中60例SCZ和60名对照的外周血样品分别混合为3份(每20个样品1份),采用全转录组测序技术获得SCZ患者与对照的外周血单个核细胞circRNAs表达谱。首先选择表达丰度较高,差异倍数≥2且有统计学意义的circRNAs,在这60例SCZ和60名对照的外周血样品中,使用实时荧光定量PCR(real-time PCR)进行验证,筛选得到与测序结果一致的circRNAs作为候选circRNAs。然后,在所有被试外周血样品中确证候选circRNAs的差异表达。结果与对照相比,SCZ患者外周血单个核细胞存在差异性表达的circRNAs共195个,其中表达上调的circRNAs有83个,表达下调的circRNAs有112个。在60例SCZ患者和60名对照的外周血样品中验证,SCZ患者circRNA_16588(circbase_id:has_circ_0004669)(0.479±0.080 vs. 1.022±0.012,P=0.003)和circRNA_12825(circbase_id:has_circ_0004442)(0.387±0.050 vs. 1.372±0.230,P=0.013)表达下调具有统计学意义,可作为候选circRNAs。在所有被试的外周血样品中对候选circRNAs进行确证,发现SCZ患者组circRNA_16588(circbase_id:has_circ_0004669)(0.583±0.050 vs. 0.910±0.060,P<0.001)和circRNA_12825(circbase_id:has_circ_0004442)(0.680±0.080 vs. 1.219±0.090,P<0.001)表达下调。结论 SCZ患者外周血单个核细胞中存在差异性表达的circRNAs,circRNA_16588和circRNA_12825在SCZ患者外周血单个核细胞中表达显著下调,有作为SCZ诊断标志物的潜力。Objective To investigate the differential expression of circRNAs in peripheral blood mononuclear cells of patients with schizophrenia, and to search for potential diagnostic markers of schizophrenia. Methods There were 175 SCZ patients and 200 healthy controls enrolled. The circRNAs expression profiles of peripheral blood mononuclear cells from schizophrenia patients and healthy controls were obtained by whole transcriptome sequencing. In small samples, the circRNAs with high expression and different multiple of ≥2 and statistical significance was selected,and 60 SCZ samples and 60 control samples were identified by real-time PCR, and circRNAs consistent with sequencing results were screened as candidate circRNAs. Then, differential expression of candidate circRNAs was confirmed in 175 SCZ and 200 control peripheral blood samples. Results One hundred ninety-five circRNAs were found to be differentially expressed in peripheral blood mononuclear cells of schizophrenia patients compared with healthy controls, among which 83 were up-regulated and 112 were down-regulated. The verification study in peripheral blood samples from 60 SCZ and 60 controls revealed that the expression levels of circRNA_16588 (circbase_id: has_circ_0004669)(0.479±0.080 vs. 1.022±0.012, P=0.003) and circRNA_12825 (circbase_id: has_circ_0004442)(0.387±0.050 vs. 1.372±0.230, P=0.013) in SCZ patient group were significantly down-regulated, which could be used as candidate circRNAs. Further confirmation of candidate circRNAs in 175 SCZ and 200 control peripheral blood samples showed that the expressions of circ RNA_ 16588 (circbase_id: has_circ_0004669)(0.583±0.050 vs. 0.910±0.060, P<0.001) and circRNA_12825 (circbase_id: has_circ_0004442)(0.680±0.080 vs. 1.219±0.090, P<0.001) in SCZ patient group were down-regulated compared with the control group. Conclusion There are differentially expressed circRNAs profiles in peripheral blood mononuclear cells of patients with schizophrenia, circRNA_16588 and circRNA_12825 are significantly down-re

关 键 词：精神分裂症 诊断标志物 外周血单个核细胞 环状RNAs 

分 类 号：R749.3[医药卫生—神经病学与精神病学]