血浆miRNA-200b 及miRNA-21 在上皮性卵巢癌中的表达及其临床意义

目的:探讨血浆微小核糖核酸-200b(miRNA-200b)及微小核糖核酸-21(miRNA-21)在上皮性卵巢癌(EOC)中的表达及其临床意义。方法:采用RT-PCR 检测162 例EOC 患者、120 例上皮性卵巢良性肿瘤患者(良性组)和108 例健康女性(对照组)血浆miRNA-200b、miRNA-21 及CA125 表达水平,分析miRNA-200b 及miRNA-21 表达水平与EOC 临床病理特征的关系。应用ROC 曲线评价miRNA-200b、miRNA-21 及CA125 对EOC 诊断的灵敏度和特异度,多元Logistic 回归模型分析三项指标与EOC 的关系。Pearson 相关分析EOC 患者血浆miRNA-200b 与miRNA-21、CA125 的相关性。结果:EOC 组血浆miRNA-200b、miRNA-21 及CA125 表达水平均明显高于良性组和对照组[miRNA-200b(2- Ct ):3.52±1.03 vs 1.26±0.37 和1.15±0.34;miRNA-21(2- Ct):2.32±0.45 vs 1.18±0.32 和1.04±0.28;CA125(U/ ml):78.64±30.57 vs 26.27±11.36 和21.53±9.45,均P <0.01]。血浆miRNA-200b、miRNA-21、CA125 及三项联合诊断EOC 的AUC(95% CI) 分别为0.896(0.834 ~0.958)、0.792(0.731 ~0.847)、0.908(0.841 ~ 0.973)、0.947(0.883 ~ 0.995),其最佳截值分别为2.08、1.46、52.84 U/ ml。Logistic 回归分析显示,血浆miRNA-200b、miRNA-21 及CA125 水平升高是EOC 发生的独立危险因素[OR(95% CI)= 2.518(1.563 ~3.547),OR(95%CI)= 1.724(1.103 ~ 2.528),OR(95% CI)= 2.316(1.347 ~ 3.419)]。EOC 患者血浆miRNA-200b与CA125 的相关性最好(r =0.702,P<0.01)。结论:血浆miRNA-200b 及miRNA-21 可作为早期诊断EOC 的分子标志物,其诊断效能与CA125 相当,三项联合应用有望提高EOC 早期诊断的准确性。

Expression of plasma miRNA-21 and miRNA-200b in epithelial ovarian cancer and its clinical significance

Objective:To investigate the expression and clinical significance of plasma microRNA-21 (miRNA-21) and microRNA-200b (miRNA-200b) in epithelial ovarian cancer (EOC).Methods:The levels of plasma miRNA-200b,miRNA-21 and CA125 were detected by RT-PCR in 162 patients with EOC,120 patients with benign epithelial ovarian tumors (benign group) and 108 healthy women (control group),analyze the relation between miRNA-200b and miRNA-21 expression and clinicopathological features of EOC.The sensitivity and specificity of miRNA-200b,miRNA-21 and CA125 to EOC diagnosis were evaluated by ROC curve,and the relationship between three indexes and EOC was analyzed by multivariate Logistic regression model.Correlation analysis of plasma miRNA-200b and miRNA-21,CA125 in patients with EOC by Pearson correlation.Results:The levels of plasma miRNA-200b,miRNA-21 and CA125 in EOC group were significantly higher than those in benign group and control group[miRNA-200b(2- Ct):3.52±1.03 vs 1.26±0.37 and 1.15±0.34;miRNA-21(2- Ct ):2.32±0.45 vs 1.18±0.32 and 1.04±0.28;CA125(U/ ml):78.64±30.57 vs 26.27±11.36 and 21.53±9.45,all P<0.01].Plasma miRNA-200b,miRNA-21,CA125 and three combined diagnosis EOC of AUC (95%CI) were0.896(0.834-0.958),0.792(0.731-0.847),0.908(0.841-0.973),0.947(0.883-0.995),the optimal cut-off values were 2.08,1.46,52.84 U/ ml.Logistic regression analysis showed that elevated plasma levels of miRNA-200b,miRNA-21 and CA125 were independent risk factors for EOC[OR(95% CI)= 2.518(1.563-3.547),OR(95% CI)= 1.724(1.103-2.528),OR (95%CI)= 2.316(1.347-3.419)].The correlation between plasma miRNA-200b and CA125 in patients with EOC was the best(r =0.702,P<0.01).Conclusion:Plasma miRNA-200b and miRNA-21 can be used as molecular markers for the early diagnosis of EOC, and their diagnostic efficacy is comparable to that of CA125.The combined use of the three methods is expected to improve the accuracy of early diagnosis of EOC.