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微小RNA启动子甲基化：一种准确检测尿路上皮癌的新工具。

MicroRNA promoter methylation: a new tool for accurate detection of urothelial carcinoma.

作者信息

Padrão Nuno André, Monteiro-Reis Sara, Torres-Ferreira Jorge, Antunes Luís, Leça Luís, Montezuma Diana, Ramalho-Carvalho João, Dias Paula C, Monteiro Paula, Oliveira Jorge, Henrique Rui, Jerónimo Carmen

机构信息

Cancer Biology and Epigenetics Group - Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), Rua Dr António Bernardino de Almeida, Porto 4200-072, Portugal.

Department of Pathology, Portuguese Oncology Institute of Porto (IPO Porto), Rua Dr António Bernardino de Almeida, Porto 4200-072, Portugal.

出版信息

Br J Cancer. 2017 Feb 28;116(5):634-639. doi: 10.1038/bjc.2016.454. Epub 2017 Jan 12.

DOI:10.1038/bjc.2016.454
PMID:28081549
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5344289/
Abstract

BACKGROUND

Urothelial carcinoma (UC) is the most common cancer affecting the urinary system, worldwide. Lack of accurate early detection tools entails delayed diagnosis, precluding more efficient and timely treatment. In a previous study, we found that miR-129-2 and miR-663a were differentially methylated in UC compared with other genitourinary tract malignancies. Here, we evaluated the diagnostic performance of those microRNAs in urine.

METHODS

Promoter methylation levels of miR-129-2 and miR-663a were assessed, using real-time quantitative methylation-specific PCR, in UC tissue samples (using normal urothelium as control) and, subsequently, in urine samples from UC and other genitourinary malignancies. Diagnostic and prognostic performances were evaluated by receiver operator characteristics curve and survival analyses, respectively.

RESULTS

Promoter methylation levels of both microRNAs were significantly higher in UC tissue samples compared with normal urothelium. In urine, the assay was able to distinguish UC from other genitourinary tract carcinomas with 87.7% sensitivity and 84% specificity, resulting in 85.85% overall accuracy.

CONCLUSIONS

This panel of miRNAs promoter methylation accurately detects UC in urine, comparing well with other promising epigenetic-based biomarkers. This may constitute the basis for a non-invasive assay to detect UC.

摘要

背景

尿路上皮癌（UC）是全球影响泌尿系统最常见的癌症。缺乏准确的早期检测工具导致诊断延迟，排除了更有效和及时的治疗。在先前的一项研究中，我们发现与其他泌尿生殖道恶性肿瘤相比，miR-129-2和miR-663a在UC中存在差异甲基化。在此，我们评估了这些 microRNA 在尿液中的诊断性能。

方法

使用实时定量甲基化特异性PCR评估UC组织样本（以正常尿路上皮为对照）以及随后UC和其他泌尿生殖系统恶性肿瘤尿液样本中miR-129-2和miR-663a的启动子甲基化水平。分别通过受试者工作特征曲线和生存分析评估诊断和预后性能。

结果

与正常尿路上皮相比，UC组织样本中两种 microRNA 的启动子甲基化水平均显著更高。在尿液中，该检测方法能够以87.7%的灵敏度和84%的特异性将UC与其他泌尿生殖道癌区分开来，总体准确率为85.85%。

结论

这组miRNA启动子甲基化能够准确检测尿液中的UC，与其他有前景的基于表观遗传学的生物标志物相比效果良好。这可能构成一种检测UC的非侵入性检测方法的基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5596/5344289/e2cdd44c9a45/bjc2016454f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5596/5344289/4de28ad14368/bjc2016454f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5596/5344289/299ea2dfe12c/bjc2016454f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5596/5344289/e2cdd44c9a45/bjc2016454f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5596/5344289/4de28ad14368/bjc2016454f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5596/5344289/299ea2dfe12c/bjc2016454f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5596/5344289/e2cdd44c9a45/bjc2016454f3.jpg

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