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EV-Associated miRNAs from Peritoneal Lavage are a Source of Biomarkers in Endometrial Cancer.

Berta Roman-Canal | Cristian Pablo Moiola | Sònia Gatius | Sarah Bonnin | Maria Ruiz-Miró | Esperanza González | Xavier González-Tallada | Ivanna Llordella | Isabel Hernández | José M Porcel | Antonio Gil-Moreno | Juan M Falcón-Pérez | Julia Ponomarenko | Xavier Matias-Guiu | Eva Colas
Cancers | 2019

Endometrial cancer (EC) is the sixth most common cancer in women worldwide and is responsible for more than 89,000 deaths every year. Mortality is associated with presence of poor prognostic factors at diagnosis, i.e., diagnosis at an advanced stage, with a high grade and/or an aggressive histology. Development of novel approaches that would permit us to improve the clinical management of EC patients is an unmet need. In this study, we investigate a novel approach to identify highly sensitive and specific biomarkers of EC using extracellular vesicles (EVs) isolated from the peritoneal lavage of EC patients. EVs of peritoneal lavages of 25 EC patients were isolated and their miRNA content was compared with miRNAs of EVs isolated from the ascitic fluid of 25 control patients. Expression of the EV-associated miRNAs was measured using the Taqman OpenArray technology that allowed us to detect 371 miRNAs. The analysis showed that 114 miRNAs were significantly dysregulated in EC patients, among which eight miRNAs, miRNA-383-5p, miRNA-10b-5p, miRNA-34c-3p, miRNA-449b-5p, miRNA-34c-5p, miRNA-200b-3p, miRNA-2110, and miRNA-34b-3p, demonstrated a classification performance at area under the receiver operating characteristic curve (AUC) values above 0.9. This finding opens an avenue for the use of EV-associated miRNAs of peritoneal lavages as an untapped source of biomarkers for EC.

Pubmed ID: 31216648

Research resources used in this publication

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Antibodies used in this publication

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Associated grants

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Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


miRNAMap (tool)

RRID:SCR_003156

A database of experimentally verified microRNAs and miRNA target genes in human, mouse, rat, and other metazoan genomes. In addition to known miRNA targets, three computational tools previously developed, such as miRanda, RNAhybrid and TargetScan, were applied for identifying miRNA targets in 3'-UTR of genes. In order to reduce the false positive prediction of miRNA targets, several criteria are supported for filtering the putative miRNA targets. Furthermore, miRNA expression profiles can provide valuable clues for investigating the properties of miRNAs, such tissue specificity and differential expression in cancer/normal cell. Therefore, we performed the Q-PCR experiments for monitoring the expression profiles of 224 human miRNAs in eighteen major normal tissues in human. The cross-reference between the miRNA expression profiles and the expression profiles of its target genes can provide effective viewpoint to understand the regulatory functions of the miRNA.

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HTqPCR (tool)

RRID:SCR_003375

Software package for the analysis of Ct values from high throughput quantitative real-time PCR (qPCR) assays across multiple conditions or replicates. The input data can be from spatially-defined formats such ABI TaqMan Low Density Arrays or OpenArray; LightCycler from Roche Applied Science; the CFX plates from Bio-Rad Laboratories; conventional 96- or 384-well plates; or microfluidic devices such as the Dynamic Arrays from Fluidigm Corporation. HTqPCR handles data loading, quality assessment, normalization, visualization and parametric or non-parametric testing for statistical significance in Ct values between features (e.g. genes, microRNAs).

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PANTHER (tool)

RRID:SCR_004869

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Bioconductor (tool)

RRID:SCR_006442

Software repository for R packages related to analysis and comprehension of high throughput genomic data. Uses separate set of commands for installation of packages. Software project based on R programming language that provides tools for analysis and comprehension of high throughput genomic data.

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RRID:SCR_008452

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RRID:SCR_008539

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TargetScan (tool)

RRID:SCR_010845

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RRID:SCR_010853

Catalogs of predicted microRNA targets in worm (based on ce6 genome assembly), fly (dm3), mouse (mm9) and human (hg18). We follow standard seed parameter settings and consider seeds of length 6-8 bases, beginning at position 2 of the microRNA. No mismatches or loops are allowed, but a single G:U wobble is allowed in 7- or 8-mers. In genes missing a 3' UTR annotation, 500 bp (fly), 800 bp (human and mouse) or 300 bp (worm) downstream of the annotated end of the coding sequence were used as the predicted UTR. For each organism, a catalog with zero flank and with a flank of 3 and 15 bases upstream and downstream.

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LIMMA (tool)

RRID:SCR_010943

Software package for the analysis of gene expression microarray data, especially the use of linear models for analyzing designed experiments and the assessment of differential expression.

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