血浆环状RNA hsa_circ_0032931对心房颤动射频导管消融术后复发的预测价值

Predictive value of plasma hsa_circ_0032931 for the recurrence of atrial fibrillation after radiofrequency catheter ablation

目的探讨心房颤动(房颤)患者血浆环状RNA表达谱以及在导管射频消融术后复发中的预测价值。方法研究纳入2017年12月至2018年7月在南京医科大学第一附属医院心血管内科住院房颤患者:为使用RNA测序来构建环状RNA表达谱,纳入5例特发性持续性房颤患者为测序组,同期5例基线资料一致的健康者为测序对照组;为通过实时定量聚合酶链反应(qRT-PCR)来验证房颤相关环状RNA表达,连续纳入71例特发性房颤患者为验证组,80例非房颤患者为验证对照组;为观察房颤消融术后复发情况,纳入首次行导管射频消融手术的特发性房颤患者51例,术后随访1年后分为复发组和未复发组,qRT-PCR检测特定环状RNA的表达量,并通过受试者工作特性曲线预测对消融复发的影响。结果房颤特异性的血浆环状RNA表达谱包含31697个房颤特异性环状RNA,其中516个环状RNA具有差异性表达,包括129个表达上调和387个表达下调。房颤患者环状RNA hsa_circ_0032931[0.018(0.012,0.034)对0.079(0.053,0.108),Z=-9.112;P<0.001]和hsa_circ_0032097[0.031(0.018,0.046)对0.037(0.030,0.053),Z=-2.986;P<0.05]表达水平显著降低。随访1年后,房颤消融手术复发组6例(11.8%,6/51)和未复发组45例(88.2%,45/51)发现,消融术后复发组患者血浆中环状RNA hsa_circ_0032931表达量升高[0.052(0.019,0.109)对0.016(0.012,0.030),Z=-2.573;P=0.01],而环状RNA hsa_circ_0032097表达未见明显差异(Z=-0.058;P=0.953)。根据受试者工作特性曲线分析结果,房颤持续时间的曲线下面积(AUC)为0.867(95%CI 0.706~1.000),环状RNA hsa_circ_0032931的AUC为0.826(95%CI 0.662~0.990),联合房颤持续时间与环状RNA hsa_circ_0032931的AUC为0.933(95%CI 0.841~1.000)。结论血浆环状RNA hsa_circ_0032931可作为预测房颤导管射频消融术后复发新的生物标志物和独立的预测因素。

Objective To characterize the plasma circRNAs expression profiling in atrial fibrillation(AF)patients,and explore the predictive value of specific plasma circRNAs in AF recurrence after catheter radiofrequency ablation.Methods We enrolled five idiopathic persistent AF patients(sequencing group)and five healthy persons(sequencing control group)in the First Affiliated Hospital of Nanjing Medical University from December 2017 to July 2018 to construct the circRNAs expression profiling by RNA sequencing.Seventy-one patients with idiopathic AF(validation group)and eighty non-AF individuals(validation control group)were enrolled,and to validate the expression of AF-related circRNAs by quantitative real-time polymerase chain reaction(qRT-PCR).Fifty-one AF patients were underwent catheter ablation and followed up for 1 year after ablation.One year later,these patients were divided into into recurrent group and non-recurrent group and qRT-PCR was used to test the candidate circRNAs.Receiver operating characteristic(ROC)curve were set up,and used to assess the predictive function of the selected circRNAs for predicting the recurrence of AF.Results The AF specific plasma circ RNAs expression profile contained 31697 AF-specific circRNAs,of which 516 were differentially expressed(129 upregulated and 387 downregulated).Compared with control group,plasma levels of hsa_circ_0032931[0.018(0.012,0.034)vs.0.079(0.053,0.108),Z=-9.112;P<0.001]and hsa_circ_0032097[0.031(0.018,0.046)vs.0.037(0.030,0.053),Z=-2.986;P<0.05]were significantly reduced in AF patients.During 1-year follow-up,plasma hsa_circ_0032931 in recurrent patients was significantly increased[0.052(0.019,0.109)vs.0.016(0.012,0.030),Z=-2.573;P=0.01].However,there was no significant difference in plasma hsa_circ_0032097 between recurrence and non-recurrence patients(Z=-0.058;P=0.953).Based on ROC curve analysis,the AUC of AF duration was 0.867(95%CI 0.706-1.000).And the AUC was 0.826(95%CI 0.662-0.990)for the plasma hsa_circ_0032931 as a single predictor.Notably,when AF duration was used in combination with hsa_circ_0032931,the AUC increased to 0.933(95%CI 0.841-1.000).Conclusion Plasma hsa_circ_0032931 can be served as a novel biomarker and independent predictor of AF recurrence after ablation.