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BMC Cancer
Published in: BMC Cancer 1/2017

Open Access 01-12-2017 | Research article

Identifying factors associated with the direction and significance of microRNA tumor-normal expression differences in colorectal cancer

Authors: John R. Stevens, Jennifer S. Herrick, Roger K. Wolff, Martha L. Slattery

Published in: BMC Cancer | Issue 1/2017

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Abstract

Background

microRNAs are small non-protein-coding RNA molecules that regulate gene expression, and have a potential epigenetic role in disease progression and survival of colorectal cancer. In terms of tumor-normal expression differences, many microRNAs exhibit evidence of being up-regulated in some subjects but down-regulated in others, or are dysregulated only for a subset of the population. We present and implement an approach to identify factors (lifestyle, tumor molecular phenotype, and survival-related) that are associated with the direction and/or significance of these microRNAs’ tumor-normal expression differences in colorectal cancer.

Methods

Using expression data for 1394 microRNAs and 1836 colorectal cancer subjects (each with both tumor and normal samples), we perform a dip test to identify microRNAs with multimodal distributions of tumor-normal expression differences. For proximal, distal, and rectal tumor sites separately, these microRNAs are tested for tumor-normal differential expression using a signed rank test, both overall and within levels of each lifestyle, tumor molecular phenotype, and survival-related factor. Appropriate adjustments are made to control the overall FDR.

Results

We identify hundreds of microRNAs whose direction and/or significance of tumor-normal differential expression is associated with one or more lifestyle, tumor molecular phenotype, or survival-related factors.

Conclusions

The results of this study demonstrate the benefit to colorectal cancer researchers to consider multiple subject-level factors when studying dysregulation of microRNAs, whose tumor-related changes in expression can be associated with multiple factors. Our results will serve as a publicly-available resource to provide clarifying information about various factors associated with the direction and significance of tumor-normal differential expression of microRNAs in colorectal cancer.
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Metadata
Title
Identifying factors associated with the direction and significance of microRNA tumor-normal expression differences in colorectal cancer
Authors
John R. Stevens
Jennifer S. Herrick
Roger K. Wolff
Martha L. Slattery
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-017-3690-x

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