乳腺癌患者血清中miRNA-21、miRNA-210、miRNA-1246 的表达及临床意义

Expression and diagnostic significance of miRNA-21,miRNA-210 and miRNA-1246 in breast cancer

摘要:

目的 研究血清miRNA 在乳腺癌（BC）患者及正常人群血清中的表达情况及临床诊断中的价 值。方法 收集BC 患者及健康体检者血清，通过实时荧光定量PCR（qRT-PCR）检测各组miRNA-21、 miRNA-210、miRNA-1246 的表达情况。分析单个血清miRNA 及多个血清miRNA 联合检测对BC 的诊断价 值。结果 与健康体检者比较，BC 患者血清中miRNA-21、miRNA-210、miRNA-1246 表达均增加（均P = 0.000），且3 者在BC III 期患者或有淋巴结转移的患者中高表达（P <0.05）。血清miRN-A21、miRNA-210、 miRNA-1246 诊断BC 患者的受试者工作特征曲线下面积（AUC）分别为0.936（95%CI ：0.866，0.976）、 0.980（95%CI ：0.928，0.998）、0.737（95%CI ：0.638，0.822），特异性为0.854（95%CI ：0.722，0.939）、0.917 （95%CI ：0.857，0.995）、0.583（95%CI ：0.432，0.724）。且miRNA-210 和miRNA-1246 联合检测，miRNA-21、 miRNA-210 和miRNA-1246 联合检测的诊断效能并不优于miRNA-210 单独检测。Fisher 判别分析建立BC 的最佳诊断模型，该模型排除非患者的能力较好，而发现患者的能力相对较弱（敏感性为62.5% ；特异性为 100.0%）。结论 miRNA-21、miRNA-210、miRNA-1246 在BC 患者血清中高表达，miRNA-210 单独诊断效 能较好，血清miR-210 可能是一种理想的BC 诊断标志物。

Abstract:

Objective To investigate the expression of miRNA in breast cancer (BC) patients and potential as diagnostic biomarkers. Methods Totally 48 BC patients as well as healthy volunteers were involved in this study. The levels of serum miRNA-21, miRNA-210 and miRNA-1246 were detected by RT-PCR. Diagnostic capability of miRNA were analyzed. Results Compared with normal subjects, levels of serum miRNA-21, miRNA-210 and miRNA-1246 were increased significantly in BC patients (P = 0.000), especially in patients on stage III or patients with lymph node metastasis (P < 0.05). ROC curve analyses indicated that AUC value of miRNA-21, miRNA-210 and miRNA-1246 was 0.936 (95% CI: 0.866, 0.976), 0.980 (95% CI: 0.928, 0.998) and 0.737 (95% CI: 0.638, 0.822), respectively. The specificity of miRNA-21, miRNA-210 and miRNA-1246 was 0.854 (95% CI: 0.722, 0.939), 0.917 (95% CI: 0.800, 0.977) and 0.583 (95% CI: 0.432, 0.724), respectively. Further analyses showed that, in terms of diagnostic capability, combination of miRNA-210 and miRNA-1246 or combination of miRNA-21, miRNA-210, and miRNA-1246 is not superior to miRNA-210 only. Fisher discriminant analysis established the best diagnostic model for BC, whose specificity is 100.0%. Conclusion miRNA-21, miRNA-210 and miRNA-1246 are highly expressed in breast cancer patients. Serum miR-210 may be an ideal diagnostic biomarker for BC.