Department of Cancer Biology, City of Hope Beckman Research Institute, 1500 Duarte Road, Duarte, CA 91010, USA.
J Transl Med. 2012 Mar 8;10:42. doi: 10.1186/1479-5876-10-42.
MicroRNAs (miRNAs) have been recently detected in the circulation of cancer patients, where they are associated with clinical parameters. Discovery profiling of circulating small RNAs has not been reported in breast cancer (BC), and was carried out in this study to identify blood-based small RNA markers of BC clinical outcome.
The pre-treatment sera of 42 stage II-III locally advanced and inflammatory BC patients who received neoadjuvant chemotherapy (NCT) followed by surgical tumor resection were analyzed for marker identification by deep sequencing all circulating small RNAs. An independent validation cohort of 26 stage II-III BC patients was used to assess the power of identified miRNA markers.
More than 800 miRNA species were detected in the circulation, and observed patterns showed association with histopathological profiles of BC. Groups of circulating miRNAs differentially associated with ER/PR/HER2 status and inflammatory BC were identified. The relative levels of selected miRNAs measured by PCR showed consistency with their abundance determined by deep sequencing. Two circulating miRNAs, miR-375 and miR-122, exhibited strong correlations with clinical outcomes, including NCT response and relapse with metastatic disease. In the validation cohort, higher levels of circulating miR-122 specifically predicted metastatic recurrence in stage II-III BC patients.
Our study indicates that certain miRNAs can serve as potential blood-based biomarkers for NCT response, and that miR-122 prevalence in the circulation predicts BC metastasis in early-stage patients. These results may allow optimized chemotherapy treatments and preventive anti-metastasis interventions in future clinical applications.
微小 RNA（miRNAs）最近在癌症患者的循环中被检测到，它们与临床参数相关。在乳腺癌（BC）中尚未报道循环小 RNA 的发现分析，本研究旨在鉴定 BC 临床结果的血液小型 RNA 标志物。
对 42 例接受新辅助化疗（NCT）后接受手术肿瘤切除的局部晚期和炎症性 BC 患者的治疗前血清进行分析，通过对所有循环小 RNA 进行深度测序来进行标记物鉴定。使用 26 例 II-III 期 BC 患者的独立验证队列来评估鉴定 miRNA 标志物的能力。
在循环中检测到 800 多种 miRNA 物种，观察到的模式与 BC 的组织病理学特征相关。鉴定出与 ER/PR/HER2 状态和炎症性 BC 相关的循环 miRNA 组。通过 PCR 测量的选定 miRNA 的相对水平与其通过深度测序确定的丰度一致。两种循环 miRNA，miR-375 和 miR-122，与临床结果（包括 NCT 反应和转移性疾病复发）具有强烈相关性。在验证队列中，循环 miR-122 水平较高可特异性预测 II-III 期 BC 患者的转移性复发。
我们的研究表明，某些 miRNA 可以作为 NCT 反应的潜在血液生物标志物，而循环 miR-122 的存在可预测早期 BC 患者的转移。这些结果可能允许在未来的临床应用中优化化疗治疗和预防转移干预。
