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鉴定血液和尿液中的 microRNAs 作为膀胱癌检测的肿瘤标志物。

Identification of microRNAs in blood and urine as tumour markers for the detection of urinary bladder cancer.

机构信息

Department of Urology, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany.

出版信息

Oncol Rep. 2013 Oct;30(4):1949-56. doi: 10.3892/or.2013.2621. Epub 2013 Jul 18.

DOI:10.3892/or.2013.2621
PMID:23877086
Abstract

Since differential expression of microRNAs (miRNAs) has been found to be highly associated with several types of cancer, the goal of the present study was to identify an miRNA fingerprint as a non‑invasive diagnostic tool to detect urinary bladder cancer using the easily accessible samples of whole blood and urine. Blood and urine samples from 4 controls and from patients suffering from superficial and invasive bladder cancer were analyzed using miRNA microarray consisting of 754 human miRNAs from the Sanger database v14. Using RT‑qPCR technique, 6 of the differentially expressed miRNAs were validated in the controls (20 blood, 19 urine samples) and patients with superficial (18 blood, 16 urine samples) or invasive (20 blood and urine samples each) tumours. Three blood miRNAs (miR‑26b‑5p, miR‑144‑5p, miR‑374‑5p) were found to be significantly upregulated in invasive bladder tumour patients (P<0.05) when compared to the control group. The expression of 2 miRNAs (miR‑618, miR‑1255b‑5p) in the urine of patients with invasive tumours was significantly (P<0.05) increased in comparison to the control group. Blood miR‑26b‑5p detected the presence of invasive bladder tumours with 94% specificity and 65% sensitivity. The urine miR‑1255b‑5p reached 68% specificity and 85% sensitivity in the diagnosis of invasive tumours. This pilot study represents the first characterization of an miRNA profile for urinary bladder tumours in whole blood samples. In addition, it was shown that invasive bladder tumours could be identified by differentially expressed urine miRNAs. Further studies are needed to test the clinical usefulness for bladder cancer detection and surveillance.

摘要

由于微小 RNA(miRNA)的差异表达已被发现与多种类型的癌症高度相关,本研究的目的是确定 miRNA 指纹图谱作为一种非侵入性诊断工具,以利用易于获取的全血和尿液样本检测膀胱癌。采用包含 Sanger 数据库 v14 中 754 个人 miRNA 的 miRNA 微阵列,对 4 名对照者和患有浅表性及浸润性膀胱癌患者的血液和尿液样本进行分析。采用 RT-qPCR 技术,在对照者(20 份血液、19 份尿液样本)和患有浅表性(18 份血液、16 份尿液样本)或浸润性(每份 20 份血液和尿液样本)肿瘤的患者中验证了 6 个差异表达的 miRNA。发现 3 个血液 miRNA(miR-26b-5p、miR-144-5p、miR-374-5p)在浸润性膀胱癌患者中显著上调(P<0.05)。与对照组相比,浸润性肿瘤患者尿液中 2 个 miRNA(miR-618、miR-1255b-5p)的表达显著增加(P<0.05)。血液 miR-26b-5p 检测浸润性膀胱癌的特异性为 94%,敏感性为 65%。尿液 miR-1255b-5p 在诊断浸润性肿瘤时的特异性为 68%,敏感性为 85%。本初步研究代表了首次对全血样本中膀胱癌 miRNA 图谱进行了描述。此外,还表明可以通过差异表达的尿液 miRNA 来识别浸润性膀胱癌。需要进一步的研究来测试其在膀胱癌检测和监测中的临床实用性。

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