目的：寻找可作为乳腺癌敏感生物标志物的循环miRNA。方法：首先用qRT-PCR 方法测定80 例乳腺癌患者与80 例健康对照者循环中6 个候选miRNA（miR-9、miR-335、miR-205、miR-10b、miR-125b、miR-34a）中表达水平，筛选出改变显著的miRNA；然后再次收集80 例乳腺癌患者和80 例健康对照者，进一步验证筛选出的miRNA，并通过受试者工作特征（ROC）曲线的曲线下面积（AUC）分析这些miRNA 诊断乳腺癌的准确度，并与CA15-3 比较。结果：筛选与验证均显示，与健康对照者比较，乳腺癌患者循环miR-9 水平明显升高，而miR-335与miR-205 明显降低（均P<0.05）；miR-9、miR-335、miR-205 的诊断乳腺癌的AUC 分别为0.859（95% CI=0.814~0.911），0.920（95% CI=0.885~0.959）、0.899（95% CI=0.861~0.939）， 且miR-9、miR-335 和miR-205 联合检测的AUC 值（0.924，95% CI=0.895~0.953）明显高于CA15-3 的AUC 值（0.874，95% CI=0.834~0.914）（P<0.05）。结论：循环miR-9、miR-335、miR-205 是乳腺癌的敏感生物标志物，且联合检测更有利于提高乳腺癌诊断的准确率。
Screening and verification of circulating miRNA biomarkers of breast cancer
Objective: To seek the circulating miRNAs that can be used as sensitive biomarkers of breast cancer. Methods: Firstly, the expression levels of six candidate miRNAs (miR-9, miR-335, miR-205, miR-10b, miR-125b, and miR-34a) in blood circulation of 80 breast cancer patients and 80 healthy control subjects were measured by qRT-PCR, to screen out the miRNAs that changed significantly. Then, in another population of 80 breast cancer patients and 80 healthy control subjects, the miRNAs that were screened out were verified, and their diagnostic accuracy for breast cancer were analyzed through the area under the curve (AUC) of receiver operating characteristics (ROC) curve, which were also compared with that of A15-3. Results: Both screening and verification showed that the circulating level of miR-9 was increased while the circulating levels of miR-335 and miR-205 were decreased significantly in breast cancer patients compared with celhealthy controls (all P<0.05). The AUC of miR-9, miR-335 and miR-205 for diagnosis of breast cancer was 0.859 (95% CI=0.814–0.911), 0.920 (95% CI=0.885–0.959) and 0.899 (95% CI=0.861–0.939) respectively, and the AUC value of the combined detection of the three miRNAs (0.924, 95% CI=0.895–0.953) was significantly higher than that of CA15-3 (0.874, 95% CI=0.834–0.914) (P<0.05). Conclusion: Circulating miR-9, miR-335 and miR-205 are sensitive biomarkers for breast cancer, and their combined detection may help improve the diagnostic accuracy of breast cancer.