Novel circulating microRNA signature as a potential non-invasive multi-marker test in ER-positive early-stage breast cancer: a case control study.

Novel circulating microRNA signature as a potential non-invasive multi-marker test in ER-positive early-stage breast cancer: a case control study.
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DOI:
10.1016/j.molonc.2014.03.002
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发表时间:
2014-07
期刊:
影响因子:
6.6
通讯作者:
Ditzel HJ
Ditzel HJ
中科院分区:
医学2区
文献类型:
--
作者:
Kodahl AR;Lyng MB;Binder H;Cold S;Gravgaard K;Knoop AS;Ditzel HJ

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目前没有高度敏感和特异性的微创生物标志物用于检测早期乳腺癌。微RNA(miRNAs)存在于循环中,并且可能是用于人类癌症早期诊断的独特生物标志物。本研究的目的是研究乳腺癌患者和健康对照血清中miRNAs的差异表达。使用基于LNA的定量真实的时间PCR(qRT-PCR)对48例诊断时获得的ER阳性早期乳腺癌患者(24例淋巴结阳性和24例淋巴结阴性)和24例年龄匹配的健康对照的血清进行总体miRNA分析。随后在来自60名早期乳腺癌患者和51名健康对照的111份血清样本的独立组中验证了miRNA的特征,并在GEO数据库的3个独立数据集中进一步测试了重现性。鉴定了由9种miRNA(miR-15 a、miR-18 a、miR-107、miR-133 a、miR-139 - 5 p、miR-143、miR-145、miR-365、miR-425)组成的多变量特征,其在乳腺癌患者和健康对照之间提供了相当大的区分。此外,9种miRNA标签对来自乳腺癌患者和健康对照的样品进行分层的能力在验证集中得到证实(p = 0.012),在ROC曲线分析中具有相应的AUC = 0.665。未观察到miRNA表达与肿瘤分级、肿瘤大小、绝经或淋巴结状态之间的相关性。该签名也在先前发表的早期乳腺癌循环miRNA的独立数据集中成功验证(p = 0.024)。我们在此提出了一个能够区分ER阳性乳腺癌和健康对照的9种miRNA标签。使用基于9个miRNA签名的特定算法,可以预测未来个体的风险。由于microRNA在血液成分中高度稳定,这种特征可能有助于开发基于血液的多标记物检测,以改善乳腺癌的早期检测。这种测试可能被用作筛选工具,以确定谁将受益于进一步的诊断评估的个人。早期乳腺癌中的新型循环miRNA特征可以提高乳腺癌的早期检测。风险评分反映了乳腺癌的风险。除了乳房X光检查之外,可能还有新的筛查工具。
There are currently no highly sensitive and specific minimally invasive biomarkers for detection of early‐stage breast cancer. MicroRNAs (miRNAs) are present in the circulation and may be unique biomarkers for early diagnosis of human cancers. The aim of this study was to investigate the differential expression of miRNAs in the serum of breast cancer patients and healthy controls. Global miRNA analysis was performed on serum from 48 patients with ER‐positive early‐stage breast cancer obtained at diagnosis (24 lymph node‐positive and 24 lymph node‐negative) and 24 age‐matched healthy controls using LNA‐based quantitative real‐time PCR (qRT‐PCR). A signature of miRNAs was subsequently validated in an independent set of 111 serum samples from 60 patients with early‐stage breast cancer and 51 healthy controls and further tested for reproducibility in 3 independent data sets from the GEO Database. A multivariable signature consisting of 9 miRNAs (miR‐15a, miR‐18a, miR‐107, miR‐133a, miR‐139‐5p, miR‐143, miR‐145, miR‐365, miR‐425) was identified that provided considerable discrimination between breast cancer patients and healthy controls. Further, the ability of the 9 miRNA signature to stratify samples from breast cancer patients and healthy controls was confirmed in the validation set (p = 0.012) with a corresponding AUC = 0.665 in the ROC‐curve analysis. No association between miRNA expression and tumor grade, tumor size, menopausal‐ or lymph node status was observed. The signature was also successfully validated in a previously published independent data set of circulating miRNAs in early‐stage breast cancer (p = 0.024). We present herein a 9 miRNA signature capable of discriminating between ER‐positive breast cancer and healthy controls. Using a specific algorithm based on the 9 miRNA signature, the risk for future individuals can be predicted. Since microRNAs are highly stable in blood components, this signature might be useful in the development of a blood‐based multi‐marker test to improve early detection of breast cancer. Such a test could potentially be used as a screening tool to identify individuals who would benefit from further diagnostic assessment. Novel circulating miRNA signature in early‐stage breast cancer. May improve early detection of breast cancer. A risk score reflects the risk of breast cancer. Possible new screening tool in addition to mammography.
DOI: 10.1038/nature03702
发表时间: 2005-06-09
期刊: NATURE
影响因子: 64.8
作者:
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期刊: CLINICAL CHEMISTRY
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