宫颈癌患者血浆miRNA-10b的表达及其临床意义

目的 探讨血浆微小核糖核酸-10b(miRNA-10b)在宫颈癌患者中的表达及其临床意义。方法 采用RT-PCR检测168例宫颈癌患者,68例宫颈上皮内瘤样病变(CIN)患者(CIN组)和45例健康女性(对照组)血浆miRNA-10b,鳞癌抗原(SCCA)及癌胚抗原(CEA)表达水平,分析miRNA-10b表达与宫颈癌临床病理特征的关系。应用ROC曲线评价miRNA-10b,SCCA及CEA对宫颈癌诊断的灵敏度和特异度,多元Logistic回归模型分析三项指标与宫颈癌的关系。Pearson相关分析宫颈癌患者血浆miRNA-10b与SCCA和CEA的相关性。结果 宫颈癌组血浆miRNA-10b,SCCA及CEA表达水平均明显高于CIN组和对照组miRNA-10b(2^-ΔΔCt):5.83±1.84 vs 2.64±0.92和2.38±0.75; SCCA(ng/ml):8.74±2.26 vs 1.97±0.62和0.61±0.15; CEA(ng/ml):5.71±2.15 vs 1.56±0.58和1.34±0.16,F=17.842,13.614,8.273,均P<0.01]。宫颈癌患者血浆miRNA-10b表达水平与临床分期、淋巴结转移、浸润深度及SCCA水平相关(t/F值=19.287,21.528,5.672,5.284,均P<0.05)。血浆miRNA-10b,SCCA,CEA及三项联合诊断宫颈癌的AUC(95%CI)分别为0.836(0.752～0.924),0.795(0.722～0.875),0.664(0.596～0.738)和0.882(0.794～0.958),其最佳截值分别为4.26,6.58 ng/ml和4.05 ng/ml。Logistic回归分析显示,血浆miRNA-10b和SCCA水平升高是宫颈癌发生的独立危险因素OR(95%CI)=1.816(1.629～2.483),1.427(1.206～1.975)]。宫颈癌患者血浆miRNA-10b与SCCA呈正相关(r=0.637,P<0.01)。结论 血浆miRNA-10b有望作为早期诊断宫颈癌的分子标志物,与SCCA和CEA联合应用可提高宫颈癌诊断的准确性。

Expression of Plasma miRNA-10b in Patients with Cervical Cancer and Its Clinical Significance

Abstract:Objective To investigate the expression and clinical significance of plasma microRNA-10b(miRNA-10b)in patients with cervical cancer.Methods The levels of plasma miRNA-10b, SCCAand CEA were detected by RT-PCR in 168 patients with cervical cancer,68 patients with CIN(CIN group)and 45 healthy women(control group),analyzed the relation between miRNA-10b expression and clinicopathological features of cervical cancer.The sensitivity and specificity of miRNA-10b,SCCA and CEA in the diagnosis of cervical cancer were evaluated by ROC curve,and the relationship betweenthree indexes and cervical cancer were analyzed by multivariate Logistic regression model.Correlation analysis of plasma miRNA-10b and SCCA,CEA in patients with cervical cancer was analysed by Pearson.Results The levels of miRNA-10b, SCCA and CEA in the cervical cancer group were significantly higher than those in the CIN group and the control groupmiRNA-10b(2^-ΔΔCt):5.83±1.84 vs 2.64±0.92 and 2.38±0.75; SCCA(ng/ml):8.74±2.26 vs 1.97±0.62 and 0.61±0.15; CEA(ng/ml):5.71±2.15 vs 1.56±0.58 and 1.34±0.16,F=17.842,13.614,8.273,all P<0.01].The level of plasma miRNA-10b expression was correlated with clinical stage,lymphnode metastasis,depth of invasion and SCCA level in patients with cervical cancer(t/F=19.287,21.528,5.672,5.284,P<0.05).Plasma miRNA-10b,SCCAand CEA and three combined diagnosis of cervical cancer of AUC(95%CI)were 0.836(0.752～0.924),0.795(0.722～0.875),0.664(0.596～0.738)and 0.882(0.794～0.958),respectively.The optimal cut-off values were 4.26,6.58 ng/ml and 4.05 ng/ml,respectively.Logistic regression analysis showed that elevated plasma miRNA-10b and SCCA levels were independent risk factors for cervical cancerOR(95%CI)=1.816(1.629～2.483),OR(95%CI)=1.427(1.206～1.975)].Plasma miRNA-10b was positively correlated with SCCA in patients with cervical cancer(r=0.637,P<0.01).Conclusion Plasma miRNA-10b will be expectedto be a molecular marker for the early diagnosis of cervical cancer.The combination of SCCA and CEA can improve the diagnostic accuracy of cervical cancer.