孕妇血清中miRNAs作为生物标志物用于胎儿先心病法洛四联症的产前检测  

Serum miRNAs of pregnant women as biomarkers for prenatal detection of fetal congenital heart disease—tetralogy of Fallot

作　　者：金玉霞 李素萍 艾玲 张卫华 李晶 唐萍 JIN Yu-xia;LI Su-ping;AI Ling;ZHANG Wei-hua;LI Jing;TANG Ping(Jiaxing Maternity and Child Health Care Hospital,Women and Childrens Hospital Affiliated to Jiaxing University,Jiaxing,Zhejiang 314050,China)

机构地区：[1]嘉兴市妇幼保健院嘉兴学院附属妇儿医院,浙江嘉兴314050

出　　处：《中国卫生检验杂志》2021年第16期1931-1934,1939,共5页Chinese Journal of Health Laboratory Technology

基　　金：浙江省科技厅基金项目(LGF18H040008、LGF19H04-0005);浙江省卫计委基金项目(2017KY654、2019KY-221);嘉兴学院理工类“重大科研项目和成果”培育项目(CD70117042);嘉兴市科技局基金项目(2017AY3-3044、2018AY32022);贺林院士新医学科研基金(193-31201、19331202)。

摘　　要：目的筛选孕有先天性心脏病法洛四联症胎儿母体血清差异表达的mi RNAs,确定具有潜在意义的无创胎儿先心病法洛四联症产前诊断的候选标志物。方法收集2017年1月—2019年10月,在嘉兴市妇幼保健院行产前超声检查确诊胎儿为先天性心脏病法洛氏四联症的13例孕妇为研究对象;同时选取13例正常孕妇为对照组,孕周、孕妇年龄与法洛氏四联症组相匹配。应用二代测序对研究组及对照组孕妇血清中差异表达的mi RNAs进行筛选,进一步应用q RT-PCR技术进行差异表达的mi RNAs的验证,并行生物信息学及统计学分析。结果测序结果发现,研究组与对照组差异倍数2倍以上的mi RNAs共190个。生信分析显示,GO通路主要富集在细胞形态发生调节及离子运输上;KEGG通路主要富集在MAPK及肌动蛋白细胞骨架调节。本研究经二代测序及q RT-PCR验证,发现6个mi RNAs在先心病法洛四联症组中的表达低于对照组,差异有统计学意义(P <0.05)。结论孕妇血清中6个差异表达的mi RNAs有可能作为胎儿先天性心脏病法洛四联症的无创产前诊断分子标志物,具有潜在的临床应用价值。Objective We aimed to identify the differential expression of mi RNAs in maternal serum of pregnant women with Tetralogy of Fallot( TOF) fetuses and to assess the probabilities of potential biomarker for non-invasive prenatal diagnosis of congenital heart disease( CHD). Methods Between January 2017 and December 2018,serum sample were collected from 13 pregnant women with TOF fetuses by prenatal ultrasound examination,13 cases of normal pregnant women whose gestational week and maternal age matched with the TOF group were selected as the control group. We systematically performed high-throughput sequencing followed by independent quantitative real time polymerase chain reaction( q RT-PCR) assays to screen and validate the expression profiles of maternal serum mi RNA,and bioinformatics and statistical analysis were performed.Results According to mi RNA sequencing,a total of 190 mi RNAs were found to be at least a 2-fold difference between study group and control group. Enrichment analysis with the gene ontology database indicate that regulation of cell morphogenesis and anion transport pathway associated with embryonic heart development;KEGG database showed that the two pathways were MAPK signaling pathway and regulation of actin cytoskeleton signaling pathway related to heart development. The expression of6 mi RNAs in TOF group was significant lower than in control group,with the difference statistically significant( P < 0. 05).Conclusion The 6 altered mi RNAs in maternal serum of pregnant women may be potential biomarkers for non-invasive prenatal diagnosis of fetal TOF and has latent value for clinical application.

关 键 词：先天性心脏病 法洛四联症 产前诊断 生物标志物 

分 类 号：R72[医药卫生—儿科]