Identification of Circulating MicroRNA Signatures for Breast Cancer Detection
Identification of Circulating MicroRNA Signatures for Breast Cancer Detection
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DOI：
10.1158/1078-0432.ccr-12-3401
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发表时间：
2013-08-15
影响因子：
11.5
通讯作者：
Lee, Ann Siew-Gek
中科院分区：
文献类型：
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作者：
Chan, Maurice;Liaw, Chiew Suan;Lee, Ann Siew-Gek
目的：寻找新的非侵入性乳腺癌诊断标志物.本研究的目的是使用一组亚洲中国乳腺癌患者确定循环microRNA（miRNA）的签名，并比较肿瘤和血清样本之间的miRNA谱。实验设计：使用微阵列或锁核酸实时PCR面板，对来自32例患者的配对乳腺癌肿瘤，正常组织和血清样本的miRNA进行全面分析。来自健康个体（n = 22）的血清样品也用作正常对照。结果：20种在乳腺癌肿瘤中差异表达的最显著的miRNAs包括miRNA（miR）-21、miR-10 b和miR-145，这些miRNAs在乳腺癌中表达异常。只有7个miRNAs在肿瘤和血清中过表达，表明miRNAs可能选择性地释放到血清中。有趣的是，在血清样品中差异表达的20种最显著的miRNAs中有16种是新的。miR-1、miR-92 a、miR-133 a和miR-133 b被确定为最重要的诊断标志物，并被成功验证;这些miRNAs组合的受试者工作特征曲线的曲线下面积为0.90 ~ 0.91。作为一种非侵入性诊断策略，miRNA标签的临床应用是有希望的，但应进一步验证不同亚型的乳腺癌。（C）2013年AACR。
Purpose: There is a quest for novel noninvasive diagnostic markers for the detection of breast cancer. The goal of this study is to identify circulating microRNA (miRNA) signatures using a cohort of Asian Chinese patients with breast cancer, and to compare miRNA profiles between tumor and serum samples.Experimental Design: miRNA from paired breast cancer tumors, normal tissue, and serum samples derived from 32 patients were comprehensively profiled using microarrays or locked nucleic acid real-time PCR panels. Serum samples from healthy individuals (n = 22) were also used as normal controls. Significant serum miRNAs, identified by logistic regression, were validated in an independent set of serum samples from patients (n = 132) and healthy controls (n = 101).Results: The 20 most significant miRNAs differentially expressed in breast cancer tumors included miRNA (miR)-21, miR-10b, and miR-145, previously shown to be dysregulated in breast cancer. Only 7 miRNAs were overexpressed in both tumors and serum, suggesting that miRNAs may be released into the serum selectively. Interestingly, 16 of the 20 most significant miRNAs differentially expressed in serum samples were novel. MiR-1, miR-92a, miR-133a, and miR-133b were identified as the most important diagnostic markers, and were successfully validated; receiver operating characteristic curves derived from combinations of these miRNAs exhibited areas under the curves of 0.90 to 0.91.Conclusion: The clinical use of miRNA signatures as a noninvasive diagnostic strategy is promising, but should be further validated for different subtypes of breast cancers. (C)2013 AACR.