Dataset Information

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

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.

SUBMITTER: Padrao NA

PROVIDER: S-EPMC5344289 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Publications

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

Padrão Nuno André NA Monteiro-Reis Sara S Torres-Ferreira Jorge J Antunes Luís L Leça Luís L Montezuma Diana D Ramalho-Carvalho João J Dias Paula C PC Monteiro Paula P Oliveira Jorge J Henrique Rui R Jerónimo Carmen C

British journal of cancer 20170112 5

<h4>Background</h4>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.<h4>Methods</h4>Promoter methylation levels of miR- ...[more]

PMID: 28081549

Similar Datasets

Project description:The epigenetic alteration of aberrant hypermethylation in the promoter CpG island of a gene is associated with repression of transcription. In neoplastic cells, aberrant hypermethylation is well described as a mechanism of allele inactivation of particular genes with a tumor suppressor function. To investigate the role of aberrant hypermethylation in the biology and progression of urothelial cancer, we examined 101 urothelial (transitional cell) carcinomas (UC), broadly representative of the disease at presentation, with no prior immunotherapy, chemotherapy or radiotherapy, by Infinium HM27 containing 14,495 genes. The genome-wide signature of aberrant promoter hypermethylation in UC consisted of 729 genes significant by a Wilcoxon test, hypermethylated in a CpG island within 1 kb of the transcriptional start site and unmethylated in normal urothelium from aged individuals. We examined differences in gene methylation between the two main groups of UC: the 75% that are superficial, which often recur but rarely progress, and the 25% with muscle invasion and poor prognosis. We further examined pairwise comparisons of the pathologic subgroups of high or low grade, invasive or non-invasive (pTa), and high grade superficial or low grade superficial UC. Pathways analysis indicated over-representation of genes involved in cell adhesion or metabolism in muscle-invasive UC. Notably, the TET2 epigenetic regulator was one of only two genes more frequently methylated in superficial tumors and the sole gene in low grade UC. Other chromatin remodeling genes, MLL3 and ACTL6B, also showed aberrant hypermethylation. The Infinium methylation value for representative genes was verified by pyrosequencing. An available mRNA expression data set indicated many of the hypermethylated genes of interest to be downregulated in UC. Unsupervised clustering of the most differentially methylated genes distinguished muscle invasive from superficial UC. After filtering, cluster analysis showed a CpG Island Methylator Phenotype (CIMP)-like pattern of widespread methylation in 11 (11%) tumors. Nine of these 11 tumors had hypermethylation of TET2. Our analysis provides a basis for further studies of hypermethylation in the development and progression of UC.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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