The miR-509-5p/miR-124 ratio of liquid biopsies in diagnosis of bladder cancer

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The miR-509-5p/miR-124 ratio of liquid biopsies in diagnosis of bladder cancer

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- The miR-509-5p/miR-124 ratio of liquid biopsies in diagnosis of bladder cancer
- China Oncology Vol. 27, Issue 6, Pages: 496-500(2017)
- 作者机构：
  
  复旦大学附属肿瘤医院泌尿外科，复旦大学上海医学院肿瘤学系,上海,200032
- 作者简介：
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2017.06.016
  CLC：
- Published Online：26 July 2017，
  
  Published：26 July 2017
- 稿件说明：
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沈益君,谢湖阳,万方宁,等. 液态活检miR-509-5p/miR-124比值诊断膀胱癌的临床应用[J]. 中国癌症杂志, 2017, 27(6): 496-500.

沈益君, 谢湖阳, 万方宁. The miR-509-5p/miR-124 ratio of liquid biopsies in diagnosis of bladder cancer[J]. China Oncology, 2017, 27(6): 496-500.
沈益君,谢湖阳,万方宁,等. 液态活检miR-509-5p/miR-124比值诊断膀胱癌的临床应用[J]. 中国癌症杂志, 2017, 27(6): 496-500. DOI： 10.19401/j.cnki.1007-3639.2017.06.016.

沈益君, 谢湖阳, 万方宁. The miR-509-5p/miR-124 ratio of liquid biopsies in diagnosis of bladder cancer[J]. China Oncology, 2017, 27(6): 496-500. DOI： 10.19401/j.cnki.1007-3639.2017.06.016.

摘要

背景与目的：液态活检是一种从血液、尿液等非实体生物组织中取样分析，主要用于恶性肿瘤诊断、监测及判断预后的方法。该研究通过优化尿液miRNA的提取方法，建立标准化的液态活检手段，筛选并验证膀胱癌患者尿液miRNA标志物以阐明其临床应用价值。方法：收集2014年1月—2015年9月膀胱癌患者及健康对照者的尿液，应用miRNA表达谱芯片进行筛选，在78例膀胱癌患者及23例健康对照者的晨尿中进行实时荧光定量聚合酶链反应(real-time fluorescent quantitative polymerase chain reaction，RTFQ-PCR)验证，分析液态活检的miRNA标志物与膀胱癌临床病理的关系及其诊断价值。结果：通过对6例膀胱癌及6例健康对照者的尿液miRNA表达谱进行分析，筛选出了10个miRNA有差异表达，结合既往文献报道的膀胱癌尿液miRNA标志物，我们挑选了20个miRNA进行RTFQ-PCR验证，发现miR-509-5p/miR-124比值在膀胱癌患者尿液中表达水平较健康对照者高，差异有统计学意义(P0.000 1)。尿液miR-509-5p/miR-124比值随着患者肿瘤分期和肿瘤分级的上升而升高(P=0.003)。当界值定在0.41时，miR-509-5p/miR-124比值对膀胱癌的诊断灵敏度为73.1%，特异度为82.6%，曲线下面积(area under the curve，AUC)达到0.864，比尿液脱落细胞学的诊断价值高(P=0.000 2)。结论：该研究优化了尿液miRNA的提取方法，建立了标准化的液态活检尿液miRNA标志物的检测手段，发现miR-509-5p/miR-124比值可能是膀胱癌理想的诊断标志物。

Abstract

Background and purpose: Liquid biopsy is a kind of blood

urine and other non-solid biological tissue sampling analysis

mainly for malignant tumor diagnosis

monitoring and predicting its prognosis. In this research

we optimized the extraction of miRNA in urine

established a standardized means of liquid biopsy

screened and verified the miRNA markers in patients with bladder cancer. Methods: From Jan. 2014 to Sept. 2015

we used miRNA microarray in six patients with bladder cancer and six healthy controls. Samples of 78 cases of bladder cancer and 23 healthy controls were tested by real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR) to verify the relationship between miRNA markers in liquid biopsy and clinical pathological parameters. The diagnostic value of miRNA markers was also analyzed and compared. Results: We screened 10 miRNAs differential expression in urine. Combined with previous literature

we selected 20 miRNAs to verify their expression levels in bladder cancers and healthy controls. miR-509-5p/miR-124 ratio in the urine was found higher in patients with bladder cancer than in healthy controls (P0.000 1). With the rise of miR-509-5p/miR-124 ratio in urine

tumor stage and grade were also increased (P=0.003). When the cutoff was set at 0.41

the diagnostic sensitivity and specificity of miR-509-5p/miR-124 ratio were 73.1% and 82.6%

respectively. The AUC of miR-509-5p/miR-124 ratio to detect bladder cancer was 0.864

higher than that of urinary exfoliated cells (P=0.000 2). Conclusion: We optimized the extraction of miRNAs in urine

established a standardized liquid biopsy of miRNA markers. The miR-509-5p/miR-124 ratio could be an ideal diagnostic marker for bladder cancer.

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