血浆lncRNA XIST在子宫平滑肌瘤患者中的相对表达量及其临床意义

Relative expression and clinical significance of plasma lncRNA XIST in patients with uterine leiomyoma

目的探讨血浆长链非编码RNA X-非活性特异性转录本(lncRNA XIST)在子宫平滑肌瘤(UL)患者中的相对表达量及其临床意义。方法选取2018年5月至2022年2月在该院首次接受了UL外科手术治疗的562例女性为UL组,从其中的116例患者中同时获得了UL肿块组织及癌旁组织。另招募280例妇科体检健康女性作为对照组。根据随访情况,将UL组患者进一步分为复发组与未复发组。采用实时荧光定量聚合酶链反应(RT-qPCR)分析所有研究对象的血浆lncRNA XIST相对表达量,以及116例患者UL肿块及癌旁组织中lncRNA XIST相对表达量。比较UL组与对照组、复发组与未复发组血浆lncRNA XIST相对表达量,比较UL肿块组织及癌旁组织中lncRNA XIST相对表达量。采用Pearson相关分析UL组织与血浆lncRNA XIST相对表达量的相关性。采用受试者工作特征(ROC)曲线分析血浆lncRNA XIST相对表达量对UL的诊断价值,以及对术后复发的预测价值。采用多变量Cox比例风险回归分析UL术后复发生存的影响因素。结果UL组血浆lncRNA XIST相对表达量明显高于对照组,差异有统计学意义(Z=15.732,P<0.001)。血浆lncRNA XIST诊断UL的曲线下面积(AUC)为0.948(95%CI:0.933~0.963,P<0.001)。UL肿块组织lncRNA XIST相对表达量明显高于癌旁组织,差异有统计学意义(Z=6.672,P<0.001)。UL患者血浆和UL肿块lncRNA XIST相对表达量呈正相关(r=0.198,P=0.033)。224例(43.42%)UL患者出现了疾病复发,纳入复发组,其余患者纳入未复发组。复发组血浆lncRNA XIST相对表达量明显高于未复发组,差异有统计学意义(Z=4.779,P<0.001)。血浆lncRNA XIST预测术后复发的AUC为0.618(95%CI:0.572~0.663,P<0.001)。多变量Cox比例风险回归分析结果显示,超声检查肌瘤数量、血浆lncRNA XIST相对表达量和术后残余是术后无复发生存的独立影响因素(P<0.05)。Kaplan-Meier曲线分析结果显示,与血浆lncRNA XIST≤3.483患者相比,血浆lncRNA XIST>3.483患者无复发生存时间更短(Log-rank χ^(2)=32.259,P<0.001)。结论高血浆lncRNA XIST相对表达量可能是引起UL的机制之一,此外高血浆lncRNA XIST相对表达量预示着UL患者的预后不良。

Objective To investigate the relative expression of plasma X-ray inactive long chain noncoding RNA specificity transcript(lncRNA XIST)in patients with uterine leiomyoma(UL)and its clinical significance.Methods A total of 562 women who underwent UL surgery for the first time in Ankang Maternal and Child Health Hospital from May 2018 to February 2022 were selected as the UL group,and 116 of them were obtained myoma tissue and adjacent myometrium tissue(within 2 cm of myoma)at the same time.Another 280 healthy women were recruited as the control group.According to the results of follow-up,the UL group was further divided into recurrence group and non-recurrence group.Real-time fluorescent quantitative polymerase chain reaction(RT-qPCR)was used to analyze the relative expression of lncRNA XIST in plasma of all subjects,and the relative expression of lncRNA XIST in UL masses and adjacent myometrium tissues of 116 patients.lncRNA XIST relative expression was compared between UL group and control group,between the relapse group and recurrence group plasma,between the UL myoma tissue and adjacent myometrium tissue.Pearson correlation analysis was used to analyze the correlation between the relative expression of lncRNA XIST in UL tissue and plasma.Receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of plasma lncRNA XIST relative expression for UL and the predictive value for postoperative recurrence.Cox risk ratio regression was used to analyze the influencing factors of UL postoperative recurrence-free surivival.Results The relative expression of lncRNA XIST in plasma of UL group was significantly higher than that of control group(Z=15.732,P<0.001).The area under curve(AUC)of plasma lncRNA XIST diagnosis for UL was 0.948(95%CI:0.933-0.963,P<0.001).The relative expression of lncRNA XIST in UL tumor tissue was significantly higher than that in adjacent myometrium tissue,the difference was statistically significant(Z=6.672,P<0.001).The relative expression of lncRNA XIST in plasma of UL patients correlated positively with that in UL tumors(r=0.198,P=0.033).A total of 224(43.42%)UL patients had disease recurrence and were included in the recurrence group,and the remaining patients were included in the non-recurrence group.The plasma lncRNA XIST relative expression in the recurrence group was significantly higher than that in the non-recurrence group,the difference was statistically significant(Z=4.779,P<0.001).The AUC of plasma lncRNA XIST for predicting postoperative recurrence was 0.618(95%CI:0.572-0.663,P<0.001).Cox risk ratio regression analysis showed that the number of fibroids detected by ultrasound,plasma lncRNA XIST and postoperative residual were independent influencing factors for postoperative recurrence-free surivival(P<0.05).Kaplan and Meier curve showed that patients with plasma lncRNA XIST>3.483 has lower relapse-free survival rate(Log-rank χ^(2)=33.259,P<0.001)compared with patients with plasma lncRNA XIST≤3.483.Conclusion High plasma level of lncRNA XIST may be one of the mechanisms of UL,and high level of lncRNA XIST predicts poor long-term prognosis of UL patients.