Department of Gynecology and Obstetrics, University Hospital, LMU Munich, Munich, Germany.
Laboratory for Experimental Radiology, Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital, Marchioninistr. 15, 81377, Munich, Germany.
BMC Cancer. 2018 Feb 6;18(1):141. doi: 10.1186/s12885-018-4020-7.
microRNAs (miRNAs) are considered promising cancer biomarkers, showing high reliability, sensitivity and stability. Our study aimed to identify associations between whole blood miRNA profiles, presence of circulating tumor cells (CTCs) and clinical outcome in post-operative early breast cancer patients (EBC) to assess the utility of miRNAs as prognostic markers in this setting.
A total of 48 post-operative patients, recruited in frame of the SUCCESS A trial, were included in this retrospective study and tested with a panel of 8 miRNAs (miR-10b, -19a, - 21, - 22, -20a, - 127, - 155, -200b). Additional 17 female healthy donors with no previous history of cancer were included in the study as negative controls. Blood samples were collected at different time points (pre-adjuvant therapy, post-adjuvant therapy, 2 years follow up), total RNA was extracted and the relative concentration of each miRNA was measured by quantitative PCR and compared in patients stratified on blood collection time or CTC detection. Furthermore, we compared miRNA profiles of patients, for each time point separately, and healthy donors. CTCs were visualized and quantified with immunocytochemistry analysis. Data were analyzed using non-parametric statistical tests.
In our experimental system, miR-19a, miR-22 and miR-127 showed the most promising results, differentiating patients at different time points and from healthy controls, while miR-20a, miR-21 and miR-200b did not show any difference among the different groups. miR-10b and miR-155 were never detectable in our experimental system. With respect to patients' clinical characteristics, we found a significant correlation between miR-200b and lymph node status and between miR-20a and tumor type. Furthermore, miR-127 correlated with the presence of CTCs. Finally, we found a borderline significance between Progression Free Survival and miR-19a levels.
This pilot study suggests that profiling whole blood miRNAs could help to better stratify post-operative EBC patients without any sign of metastasis to prevent later relapse or metastatic events.
microRNAs（miRNAs）被认为是有前途的癌症生物标志物，具有高可靠性、敏感性和稳定性。我们的研究旨在确定全血 miRNA 谱、循环肿瘤细胞（CTC）的存在与术后早期乳腺癌（EBC）患者临床结局之间的关联，以评估在这种情况下 miRNAs 作为预后标志物的效用。
本回顾性研究共纳入了 SUCCESS A 试验框架内的 48 名术后患者，并使用 8 个 miRNA（miR-10b、-19a、-21、-22、-20a、-127、-155、-200b）进行了检测。另外还纳入了 17 名无癌症既往史的女性健康供体作为阴性对照。在不同时间点（术前治疗、术后治疗、2 年随访）采集血样，提取总 RNA，并通过定量 PCR 测量各 miRNA 的相对浓度，并按采血时间或 CTC 检测对患者进行分层比较。此外，我们还分别比较了各时间点患者和健康供体的 miRNA 谱。使用免疫细胞化学分析可视化和定量 CTC。数据采用非参数统计检验进行分析。
在我们的实验系统中，miR-19a、miR-22 和 miR-127 显示出最有前途的结果，可区分不同时间点的患者和健康对照者，而 miR-20a、miR-21 和 miR-200b 则不能区分不同组之间的差异。miR-10b 和 miR-155 在我们的实验系统中从未检测到。关于患者的临床特征，我们发现 miR-200b 与淋巴结状态和 miR-20a 与肿瘤类型之间存在显著相关性。此外，miR-127 与 CTC 的存在相关。最后，我们发现无进展生存期与 miR-19a 水平之间存在临界显著相关性。
这项初步研究表明，全血 miRNA 谱分析有助于更好地分层术后无转移迹象的 EBC 患者，以预防后续复发或转移事件。
