Identification of microRNAs in Nipple Discharge as Potential Diagnostic Biomarkers for Breast Cancer
Identification of microRNAs in Nipple Discharge as Potential Diagnostic Biomarkers for Breast Cancer
复制标题
鉴定乳头溢液中的 microRNA 作为乳腺癌的潜在诊断生物标志物。
DOI：
10.1245/s10434-015-4586-0
复制
发表时间：
2015-12-01
影响因子：
3.7
通讯作者：
Ma, Rong
中科院分区：
文献类型：
--
作者：
Zhang, Kai;Zhao, Song;Ma, Rong
背景资料。导管内乳腺癌通常很难诊断，因为缺乏有效的检测方法。本研究的目的是揭示和验证微小RNAs(MiRNAs)在导管内乳头状瘤患者乳头分泌物中的差异表达，并确定miRNAs是一种新的潜在的乳腺癌生物标志物。乳头溢液标本来自3例导管内癌、乳腺癌和3例导管内乳头状瘤患者。使用Axon GenePix 4000B微阵列扫描仪使用一种新的标记miRNA的方法进行miRNA表达的初步筛选。用定量实时聚合酶链式反应(qRT-PCR)进一步检测21例验证样本(8例癌和13例良性肿瘤)中miRNAs的表达水平。用独立的t检验检验miRNA表达水平与乳腺癌之间的显著相关性。基因芯片分析显示，与乳头状瘤组相比，乳腺导管内癌患者中有3个miRNAs显著上调，3个miRNAs表达下调。QRT-PCR分析进一步验证了miR-4484、miR-K12-5-5p、miR-3646和miR-4732-5p这4个miRNAs可能作为乳腺癌检测的潜在肿瘤标志物。这种使用微阵列扫描仪的新方法适用于研究含有少量miRNA的乳头分泌物中的生物标志物。MiRNAs可以作为潜在的肿瘤生物标志物，有助于乳腺癌的筛查。MiR-4484、miR-K12-5-5p和miR-3646在乳头溢液中的表达上调可能是恶性乳腺癌的一个预测因素。
Background. Intraductal breast cancer is generally difficult to diagnose because of a lack of an efficient method for detection. The purpose of this study was to reveal and validate the differential expression of microRNAs (miRNAs) in nipple discharge from intraductal papilloma patients and identify miRNAs as novel potential biomarkers for primary breast cancer.Methods. Nipple discharge samples were collected from three intraductal carcinoma breast cancer patients and three intraductal papilloma patients. The initial screening of miRNA expression was performed with an Axon GenePix 4000B microarray scanner using a novel approach to label miRNAs. The expression levels of the miRNAs selected from the initial screening were further examined by quantitative real-time polymerase chain reaction (qRT-PCR) in 21 validation samples (8 carcinomas and 13 benign tumors). An independent t test was used to detect significant correlations between the miRNA expression levels and breast cancer.Results. Microarray profiling demonstrated that three miRNAs were markedly up-regulated and three miRNAs were down-regulated in the intraductal carcinoma breast cancer patients compared to the papilloma group. The qRT-PCR analysis further verified that four miRNAs (miR-4484, miR-K12-5-5p, miR-3646, and miR-4732-5p) might serve as potential tumor biomarkers for breast cancer detection.Conclusion. The novel approach of using a microarray scanner is applicable for studying biomarkers in nipple discharge containing small amounts of miRNA. miRNAs could serve as potential tumor biomarkers that can assist in breast cancer screening. Up-regulation of miR-4484, miR-K12-5-5p, and miR-3646 in nipple discharge may be a predictor of malignant breast cancer.