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乳腺癌患者尿液中微小RNA检测的可行性及其作为一种创新型非侵入性生物标志物的潜力。

Feasibility of urinary microRNA detection in breast cancer patients and its potential as an innovative non-invasive biomarker.

作者信息

Erbes Thalia, Hirschfeld Marc, Rücker Gerta, Jaeger Markus, Boas Jasmin, Iborra Severine, Mayer Sebastian, Gitsch Gerald, Stickeler Elmar

机构信息

Department of Obstetrics and Gynecology, University Medical Center Freiburg, Hugstetterstr. 55, Freiburg, 79106, Germany.

German Cancer Consortium (DKTK), Heidelberg, Germany.

出版信息

BMC Cancer. 2015 Mar 28;15:193. doi: 10.1186/s12885-015-1190-4.

Abstract

BACKGROUND

Since recent studies revealed the feasibility to detect blood-based microRNAs (miRNAs, miRs) in breast cancer (BC) patients a new field has been opened for circulating miRNAs as potential biomarkers in BC. In this pilot study, we evaluated to our knowledge for the first time whether distinct pattern of urinary miRNAs might be also applicable as innovative biomarkers for BC detection.

METHODS

Urinary miRNA expression levels of nine BC-related miRNAs (miR-21, miR-34a, miR-125b, miR-155, miR-195, miR-200b, miR-200c, miR-375, miR-451) from 24 untreated, primary BC patients and 24 healthy controls were quantified by realtime-PCR. The receiver operating characteristic analyses (ROC) and logistic regression were calculated to assess discriminatory accuracy.

RESULTS

Significant differences were found in the expression of four BC-associated miRNAs quantified as median miRNA expression levels. Urinary miR-155 levels were significantly higher in BC patients compared to healthy controls (1.49vs.0.25; p < 0.001). In contrast, compared to healthy controls, BC patients exhibited significantly lower urinary expression levels of miR-21 (2.27vs.5.07; p < 0.001), miR-125b (0.71vs.1.62; p < 0.001), and miR-451 (0.02vs.0.59 p = 0.004), respectively. The ROC including all miRNAs as well as the group of the four significant deregulated miRNAs separated BC patients from healthy controls with a very high (area under the receiver operating characteristic curve [AUC] = 0.932) and high accuracy (AUC = 0.887), respectively.

CONCLUSIONS

We were able to demonstrate for the first time the feasibility to detect distinct BC-dependent urinary miRNA profiles. The expression levels of four urinary miRNAs were specifically altered in our cohort of BC patients compared to healthy controls. This distinct pattern offers the possibility for a specific discrimination between healthy women and primary BC patients. This sustains the potential role of urinary miRNAs as non-invasive innovative urine-based biomarkers for BC detection.

摘要

背景

由于近期研究揭示了在乳腺癌(BC)患者中检测血液中微小RNA(miRNA,miRs)的可行性,循环miRNA作为BC潜在生物标志物的新领域已被开启。在这项初步研究中,据我们所知,我们首次评估了尿液miRNA的独特模式是否也可作为BC检测的创新生物标志物。

方法

通过实时聚合酶链反应对24例未经治疗的原发性BC患者和24例健康对照者的9种与BC相关的miRNA(miR-21、miR-34a、miR-125b、miR-155、miR-195、miR-200b、miR-200c、miR-375、miR-451)的尿液miRNA表达水平进行定量。计算受试者工作特征分析(ROC)和逻辑回归以评估鉴别准确性。

结果

以miRNA表达中位数水平定量的4种与BC相关的miRNA的表达存在显著差异。与健康对照相比,BC患者尿液中miR-155水平显著更高(1.49对0.25;p<0.001)。相反,与健康对照相比,BC患者尿液中miR-21(2.27对5.07;p<0.001)、miR-125b(0.71对1.62;p<0.001)和miR-451(0.02对0.59,p = 0.004)的表达水平显著更低。包括所有miRNA以及4种显著失调miRNA的组的ROC分别以非常高的准确性(受试者工作特征曲线下面积[AUC]=0.932)和高准确性(AUC = 0.887)将BC患者与健康对照区分开来。

结论

我们首次能够证明检测独特的BC依赖性尿液miRNA谱的可行性。与健康对照相比,我们的BC患者队列中4种尿液miRNA的表达水平发生了特异性改变。这种独特模式为健康女性和原发性BC患者之间的特异性鉴别提供了可能性。这支持了尿液miRNA作为用于BC检测非侵入性创新尿液生物标志物的潜在作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d4a7/4383066/0469688d33e8/12885_2015_1190_Fig1_HTML.jpg

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