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微核糖核酸（miRNA）又称小分子核糖核酸，长约18～25个核苷酸，其中一些可以调节乳腺癌基因的表达。目前，血液循环中的miRNA已被作为乳腺癌生物学预测标志。 2018年8月11日，美国癌症学会和国际抗癌联盟《癌症医学》在线发表中国医学科学院北京协和医院肿瘤医院国家肿瘤临床医学研究中心国家癌症中心徐兵河等学者的研究报告，探讨了miRNA动态变化与新辅助化疗效果的相关性，并且发现了预测新辅助化疗敏感性的早期标志。 该研究对2014年1月～2015年11月入组II期前瞻临床研究（NCT02041338）接受新辅助化疗（紫杉醇＋卡铂、紫杉醇、表柔比星＋紫杉醇）的109例可手术或局部晚期乳腺癌患者，分别于随机入组前、两轮化疗后、手术前收集血液标本进行分析，根据临床效果将患者定义为化疗敏感或不敏感。首先，通过TaqMan探针miRNA阵列对两组所选病例的入组前和手术前标本进行候选miRNA筛选。随后，通过定量实时聚合酶链反应检测所有生物标本的候选miRNA（miR-222、miR-20a、miR-451、miR-9、miR-34a、miR-155、miR-145）。最后，通过逻辑回归模型，确定入组前与两轮化疗后这些miRNA表达之比的预测值。 根据miRNA分析结果，选择了7种miRNA进行进一步验证。结果发现，对于51例激素受体阳性HER2阴性乳腺癌患者，三种miRNA（miR-222、miR-20a、miR-451）的动态变化与化疗敏感性相关。重要的是，对于所有三种乳腺癌亚型（激素受体阳性HER2阴性、HER2阳性、三阴性）始终可以发现化疗不敏感患者血浆miR-34a减少。最后，通过逻辑回归模型，确定激素受体阳性HER2阴性乳腺癌新辅助化疗效果的预测指标：
因此，该研究结果表明循环miRNA动态变化可能有助于预测乳腺癌新辅助化疗的临床效果。 Cancer Med. 2018 Aug 11. [Epub ahead of print] Dynamics of circulating microRNAs as a novel indicator of clinical response to neoadjuvant chemotherapy in breast cancer. Zhu W, Liu M, Fan Y, Ma F, Xu N, Xu B. National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. BACKGROUND: Circulating microRNAs (miRNAs) have been indicated as predictive biomarkers in breast cancer. We aimed to explore the association of plasma miRNA dynamics with response to neoadjuvant chemotherapy (NCT) and disclose early markers for predicting sensitivity. METHODS: One hundred and nine patients with operable or locally advanced breast cancer, who participated in a prospective clinical trial and received NCT, were analyzed. Blood samples were collected before random assignment, after two cycles of chemotherapy (C2) and before surgery. Based on their clinical response, the patients were defined as chemo-sensitive or insensitive. First, baseline and preoperative samples of selected cases from both groups were screened via TaqMan miRNA array for candidate miRNAs. Afterward all the biospecimens were tested for the candidate miRNAs (miR-222, miR-20a, miR-451, miR-9, miR-34a, miR-155, and miR-145) by quantitative real-time PCR. Finally, logistic regression model was utilized to determine the predictive value of baseline/C2 expression of these miRNAs. RESULTS: Based on the results of microRNA profiling, seven miRNAs were selected for further validation. In the HR+/HER2- cohort (n = 51) dynamics of three miRNAs, including miR-222, miR-20a, and miR-451, were associated with chemo-sensitivity. Importantly, across all the three subtypes we consistently identified chemo-induced decrease in plasma miR-34a in the insensitive patients. Finally, baseline miR-222 overexpression (OR = 6.422, P = 0.049), C2 miR-20a up-regulation (OR = 0.144, P = 0.021) and C2 miR-451 down-regulation (OR = 8.213, P = 0.012) were predictive markers of response to NCT in HR+/HER2- breast cancer. CONCLUSIONS: We described that dynamics of circulating miRNAs might help predict clinical response to NCT in breast cancer. KEYWORDS: breast cancer; circulating miRNAs; dynamics; neoadjuvant chemotherapy; sensitivity PMID: 30099860 DOI: 10.1002/cam4.1723
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