A pilot study of circulating miRNAs as potential biomarkers of early stage breast cancer.
A pilot study of circulating miRNAs as potential biomarkers of early stage breast cancer.
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DOI：
10.1371/journal.pone.0013735
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发表时间：
2010-10-29
期刊：
影响因子：
3.7
通讯作者：
Liu S
中科院分区：
文献类型：
--
作者：
Zhao H;Shen J;Medico L;Wang D;Ambrosone CB;Liu S
迄今为止，还没有高度敏感和特异的微创生物标志物用于早期乳腺癌检测。在癌症患者和健康对照者中反复观察到血液成分（包括血清和血浆）中存在循环 microRNA (miRNA)。由于 miRNA 在致癌过程中的重要性，血液中的循环 miRNA 可能是人类癌症早期和微创诊断的独特生物标志物。这项试点研究的目的是发现一组循环 miRNA 作为潜在的新型乳腺癌生物标志物。使用基于微阵列的表达谱分析和实时定量聚合酶循环反应 (RT-qPCR) 验证，我们比较了 20 名早期乳腺癌女性（10 名白人美国人 (CA) 和 10 名非裔美国人 (AA)）和 20 名匹配的健康对照（10 名 CA 和 10 AA）血浆样本中循环 miRNA 的水平。使用 p < 0.05 的显着性水平（受至少两倍表达变化限制）作为选择标准，我们发现 31 个 miRNA 在 CA 研究对象中差异表达（17 个向上和 14 个向下），18 个 miRNA 在 AA 研究对象中差异表达（9 个向上和 9 个向下）。有趣的是，CA 和 AA 研究对象之间只有 2 个差异表达的 miRNA 重叠。使用受试者工作曲线（ROC）分析，我们表明不仅上调的 miRNA 还可以下调的 miRNA 可以以合理的敏感性和特异性区分乳腺癌患者和健康对照。为了进一步探讨这些循环miRNA在乳腺癌发生中的潜在作用，我们应用基于通路的生物信息学探索性分析，预测了许多显着富集的通路，这些通路预计受这些循环miRNA的调节，其中大多数涉及关键的细胞功能、癌症的发生和进展。我们从这项试点研究中观察到，循环 miRNA 水平的改变可能具有作为乳腺癌早期检测的新型非侵入性生物标志物的巨大潜力。
To date, there are no highly sensitive and specific minimally invasive biomarkers for detection of breast cancer at an early stage. The occurrence of circulating microRNAs (miRNAs) in blood components (including serum and plasma) has been repeatedly observed in cancer patients as well as healthy controls. Because of the significance of miRNA in carcinogenesis, circulating miRNAs in blood may be unique biomarkers for early and minimally invasive diagnosis of human cancers. The objective of this pilot study was to discover a panel of circulating miRNAs as potential novel breast cancer biomarkers. Using microarray-based expression profiling followed by Real-Time quantitative Polymerase Cycle Reaction (RT-qPCR) validation, we compared the levels of circulating miRNAs in plasma samples from 20 women with early stage breast cancer (10 Caucasian American (CA) and 10 African American (AA)) and 20 matched healthy controls (10 CAs and 10 AAs). Using the significance level of p<0.05 constrained by at least two-fold expression change as selection criteria, we found that 31 miRNAs were differentially expressed in CA study subjects (17 up and 14 down) and 18 miRNAs were differentially expressed in AA study subjects (9 up and 9 down). Interestingly, only 2 differentially expressed miRNAs overlapped between CA and AA study subjects. Using receiver operational curve (ROC) analysis, we show that not only up-regulated but also down-regulated miRNAs can discriminate patients with breast cancer from healthy controls with reasonable sensitivity and specificity. To further explore the potential roles of these circulating miRNAs in breast carcinogenesis, we applied pathway-based bioinformatics exploratory analysis and predicted a number of significantly enriched pathways which are predicted to be regulated by these circulating miRNAs, most of which are involved in critical cell functions, cancer development and progression. Our observations from this pilot study suggest that the altered levels of circulating miRNAs might have great potential to serve as novel, noninvasive biomarkers for early detection of breast cancer.
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