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血浆中的循环 microRNAs 作为乳腺癌的早期检测标志物。

Circulating microRNAs in plasma as early detection markers for breast cancer.

机构信息

Molecular Epidemiology, German Cancer Research Center, DKFZ, Heidelberg, BW, Germany.

出版信息

Int J Cancer. 2013 Apr 1;132(7):1602-12. doi: 10.1002/ijc.27799. Epub 2012 Sep 14.

Abstract

In recent years, circulating miRNAs have attracted a great deal of attention as promising novel markers for various diseases. Here, we investigated their potential to serve as minimally invasive, early detection markers for breast cancer in blood plasma. We profiled miRNAs extracted from the plasma of early stage breast cancer patients (taken at the time-point of diagnosis) and healthy control individuals using TaqMan low-density arrays (TLDA). Selected candidates identified in the initial screen were further validated in an extended study cohort of 207 individuals including 127 sporadic breast cancer cases and 80 healthy controls via RT-qPCR. Four miRNAs (miR-148b, miR-376c, miR-409-3p and miR-801) were shown to be significantly upregulated in the plasma of breast cancer patients. ROC curve analysis showed that the combination of only three miRNAs (miR-148b, miR-409-3p and miR-801) had an equal discriminatory power between breast cancer cases and healthy controls as all four miRNAs together (AUC = 0.69). In conclusion, the identified miRNAs might be of potential use in the development of a multimarker blood-based test to complement and improve early detection of breast cancer. Such a multimarker blood test might for instance provide a prescreening tool, especially for younger women, to facilitate decisions about which individuals to recommend for further diagnostic tests.

摘要

近年来,循环 miRNA 作为各种疾病有前途的新型标志物引起了极大关注。在这里,我们研究了它们作为血浆中乳腺癌微创早期检测标志物的潜力。我们使用 TaqMan 低密度阵列 (TLDA) 对早期乳腺癌患者(在诊断时采集)和健康对照个体的血浆中提取的 miRNA 进行了分析。在包括 127 例散发性乳腺癌病例和 80 例健康对照的 207 例个体的扩展研究队列中,通过 RT-qPCR 进一步验证了初始筛选中确定的候选物。有四个 miRNA(miR-148b、miR-376c、miR-409-3p 和 miR-801)在乳腺癌患者的血浆中明显上调。ROC 曲线分析表明,仅三种 miRNA(miR-148b、miR-409-3p 和 miR-801)的组合在乳腺癌病例和健康对照之间的区分能力与所有四种 miRNA 相同(AUC = 0.69)。总之,鉴定出的 miRNA 可能在开发基于血液的多标志物检测中具有潜在用途,以补充和改善乳腺癌的早期检测。这种多标志物血液检测例如可以作为一种预筛选工具,特别是对年轻女性,可以帮助决定推荐哪些个体进行进一步的诊断测试。

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