复发性流产患者血清细胞外囊泡circRNAs的表达及临床意义  

Expression and clinical significance of circRNAs in serum extracellular vesicles of patients with recurrent spontaneous abortion

作　　者：曹相婷 崔荣淑 滕云雁 刘金 徐小飞[2] 董召刚[1] CAO Xiangting;CUI Rongshu;TENG Yunyan;LIU Jin;XU Xiaofei;DONG Zhaogang(Department of Clinical Laboratory,Qilu Hospital of Shandong University,Jinan 250012,Shandong,China;Center for Reproductive Medicine,Department of Obstetrics and Gynecology,Qilu Hospital of Shandong University,Jinan 250012,Shandong,China)

机构地区：[1]山东大学齐鲁医院,检验科,济南250012 [2]山东大学齐鲁医院,妇产科生殖医学中心,济南250012

出　　处：《临床检验杂志》2025年第3期209-214,共6页Chinese Journal of Clinical Laboratory Science

基　　金：山东省自然科学基金面上项目(ZR2021MC032);中国博士后科学基金面上项目(2020M672071)。

摘　　要：目的 分析复发性流产(recurrent spontaneous abortion,RSA)患者血清细胞外囊泡(extracellular vesicles,EVs)环状RNA(circular RNAs,circRNAs)的表达及临床意义。方法 收集2021年5月至2023年3月就诊于山东大学齐鲁医院的3例RSA患者和3例正常妊娠者(对照)血清样本,采用基因表达谱芯片筛选血清EVs中差异表达的circRNAs。收集10例RSA患者和10例对照为训练集,80例RSA患者和64例对照为验证集,利用实时荧光定量PCR(real-time quantitative polymerase chain reaction,qRT-PCR)检测两组间差异circRNAs的表达水平,采用ROC曲线评价差异circRNAs对RSA的诊断价值。结果 采用基因表达谱芯片共检测出血清EVs中存在57563个circRNAs,且与对照组相比,RSA患者中存在差异表达的为3516个(其中2377个上调,1139个下调)。qRT-PCR在训练集和验证集中的检测结果显示,RSA组血清EVs hsa_circ_0054403的表达水平[2.07(1.00,6.68)]显著高于对照组[1.00(0.42,1.46),U=1239,P<0.01];而hsa_circ_0020897[0.33(0.11,1.40)vs 1.00(0.46,3.66)]和hsa_circ_0072745[0.49(0.22,1.60)vs 1.00(0.51,7.93)]的表达水平显著低于对照组(U分别为1712和1714,P均<0.01)。ROC曲线显示,血清EVs hsa_circ_0054403、hsa_circ_0020897和hsa_circ_0072745对RSA具有较高的预测价值,其ROC曲线下面积(AUC ROC)分别为0.758、0.666、0.664,敏感性和特异性分别为47.5%和100.0%、50.0%和81.2%、62.5%和70.3%。上述3个circRNAs联合检测时,其AUC ROC为0.842,敏感性和特异性分别为73.7%和79.7%。结论 hsa_circ_0054403、hsa_circ_0020897、hsa_circ_0072745在RSA患者血清EVs中呈异常表达,可作为预测RSA的潜在标志物。Objective To investigate the expression level and clinical significance of circular RNAs(circRNAs)in serum extracellular vesicles(EVs)of patients with recurrent spontaneous abortion(RSA).Methods The serum samples from 3 RSA patients and 3 normal pregnant women(controls)visited our hospital from May 2021 to March 2023 were collected and the gene expression profiling chips were used to screen for differentially expressed circRNAs in serum EVs.Ten RSA patients and 10 normal pregnant women were enrolled in a training set and 80 RSA patients and 64 normal pregnant women were enrolled in a validation set.Real-time quantitative polymerase chain reaction(qRT-PCR)was used to detect the levels of differentially expressed circRNAs between the two groups.The predictive value of differentially expressed circRNAs for RSA was evaluated by the receiver operating characteristic(ROC)curve.Results A total of 57563 circRNAs in serum EVs were detected by the gene expression profiling chips.Compared with the control group,3516 circRNAs were differentially expressed in RSA patients,including 2377 up-regulated and 1139 down-regulated.The detection results of qRT-PCR in the training set and validation set showed that the expression levels of hsa_circ_0054403 in serum EVs of RSA patients(2.07[1.00,6.68])was significantly higher than that in the control group(1.00[0.42,1.46],U=1239,P<0.01),while those of hsa_circ_0020897(0.33[0.11,1.40]vs 1.00[0.46,3.66],U=1712,P<0.01)and hsa_circ_0072745(0.49[0.22,1.60]vs 1.00[0.51,7.93],U=1714,P<0.01)were significantly lower than that in the control group.The ROC curve showed that the hsa_circ_0054403,hsa_circ_0020897,and hsa_circ_0072745 in serum EVs had high predictive value for RSA.Their AUC ROC were 0.758,0.666,and 0.664,respectively,and the corresponding sensitivity and specificity were 47.5%and 100.0%,50.0%and 81.2%,and 62.5%and 70.3%,respectively.When the three circRNAs were combined,it′s AUC ROC,sensitivity,and specificity were 0.842,73.7%,and 79.7%,respectively.Conclusion The hsa_circ_0054403,

关 键 词：复发性流产 细胞外囊泡 circRNA 生物学标志物 

分 类 号：R446[医药卫生—诊断学]