Circulating miR-148b and miR-133a as biomarkers for breast cancer detection.

Circulating miR-148b and miR-133a as biomarkers for breast cancer detection.
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DOI:
10.18632/oncotarget.2014
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发表时间:
2014-07-30
期刊:
影响因子:
--
通讯作者:
Liu S
Liu S
中科院分区:
其他
文献类型:
--
作者:
Shen J;Hu Q;Schrauder M;Yan L;Wang D;Medico L;Guo Y;Yao S;Zhu Q;Liu B;Qin M;Beckmann MW;Fasching PA;Strick R;Johnson CS;Ambrosone CB;Zhao H;Liu S

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循环microRNA作为乳腺癌的新型生物标志物受到了广泛关注。然而,迄今为止,结果好坏参半。在这里,我们使用来自乳腺癌患者和健康对照的血浆样本进行了三阶段microRNA分析,并努力解决先前研究中观察到的检测技术和研究设计中的几个陷阱。在122名高加索研究受试者的发现阶段,我们发现了43种在乳腺癌病例和健康对照之间差异表达的microRNA。当这些microRNA与其他研究的已发表数据进行比较时,我们确定了三种microRNA,包括miR-148 b,miR-133 a和miR-409- 3 p,其血浆水平在乳腺癌病例中显著高于健康对照,并且在以前的独立研究中也很重要。在50例乳腺癌病例和50例健康对照的验证阶段,我们验证了miR-148 b和miR-133 a与乳腺癌检测的相关性(P分别为1.5×10−6和1.3×10−10)。在体外研究阶段,我们发现miR-148 b和miR-133 a均从乳腺癌细胞系中分泌,显示了它们的分泌潜力和可能的肿瘤起源。因此,我们的数据表明miR-148 b和miR-133 a都有可能用作乳腺癌检测的生物标志物。
Circulating microRNAs have drawn a great deal of attention as promising novel biomarkers for breast cancer. However, to date, the results are mixed. Here, we performed a three-stage microRNA analysis using plasma samples from breast cancer patients and healthy controls, with efforts taken to address several pitfalls in detection techniques and study design observed in previous studies. In the discovery phase with 122 Caucasian study subjects, we identified 43 microRNAs differentially expressed between breast cancer cases and healthy controls. When those microRNAs were compared with published data from other studies, we identified three microRNAs, including miR-148b, miR-133a and miR-409-3p, whose plasma levels were significantly higher in breast cancer cases than healthy controls and were also significant in previous independent studies. In the validation phase with 50 breast cancer cases and 50 healthy controls, we validated the associations with breast cancer detection for miR-148b and miR-133a (P = 1.5×10−6 and 1.3×10−10, respectively). In the in-vitro study phase, we found that both miR-148b and miR-133a were secreted from breast cancer cell lines, showing their secretory potential and possible tumor origin. Thus, our data suggest that both miR-148b and miR-133a have potential use as biomarkers for breast cancer detection.
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