De novo sequencing of circulating miRNAs identifies novel markers predicting clinical outcome of locally advanced breast cancer.
De novo sequencing of circulating miRNAs identifies novel markers predicting clinical outcome of locally advanced breast cancer.
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循环 miRNA 的从头测序鉴定出预测局部晚期乳腺癌临床结果的新标志物
DOI：
10.1186/1479-5876-10-42
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发表时间：
2012-03-08
影响因子：
7.4
通讯作者：
Wang SE
中科院分区：
文献类型：
--
作者：
Wu X;Somlo G;Yu Y;Palomares MR;Li AX;Zhou W;Chow A;Yen Y;Rossi JJ;Gao H;Wang J;Yuan YC;Frankel P;Li S;Ashing-Giwa KT;Sun G;Wang Y;Smith R;Robinson K;Ren X;Wang SE
最近在癌症患者的血液循环中检测到MicroRNAs(MiRNAs)，它们与临床参数有关。对42例接受新辅助化疗(NCT)后接受手术切除的局部晚期炎症性乳腺癌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，以确定乳腺癌临床转归的血液小RNA标志物。对26例II-III期BC患者进行了独立的验证队列，以评估所识别的miRNA标记的能力。结果在循环中检测到800多种miRNA，观察到的模式与BC的组织病理学特征有关。确定了与ER/PR/HER2状态和炎性BC不同相关的循环miRNAs组。所选miRNAs的相对水平由聚合酶链式反应测定，与其丰度的深层测序结果一致。两个循环中的miRNAs，miR-375和miR-122，与临床结果有很强的相关性，包括NCT反应和复发与转移性疾病。在验证队列中，循环中较高水平的miR-122可以特异性地预测II-III期BC患者的转移复发。结论我们的研究表明，某些miRNAs可以作为潜在的基于血液的生物标志物来预测NCT的反应，循环中miR-122的流行可以预测早期患者的BC转移。这些结果可能使优化的化疗治疗和预防性抗转移干预在未来的临床应用。
BackgroundMicroRNAs (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.MethodsThe 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.ResultsMore 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.ConclusionsOur 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.
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DOI：
10.1186/bcr2766
发表时间：
2010
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Roth C;Rack B;Müller V;Janni W;Pantel K;Schwarzenbach H
通讯作者：
Schwarzenbach H
影响因子：
3.5
作者：
El-Din, Mohamed A. Alm;Taghian, Alphonse G.
通讯作者：
Taghian, Alphonse G.
影响因子：
64.8
作者：
Burns, David M.;D'Ambrogio, Andrea;Nottrott, Stephanie;Richter, Joel D.
通讯作者：
Richter, Joel D.
影响因子：
11.2
作者：
Iorio, MV;Ferracin, M;Croce, CM
通讯作者：
Croce, CM
影响因子：
4
作者：
Kutay, Huban;Bai, Shoumei;Ghoshal, Kalpana
通讯作者：
Ghoshal, Kalpana