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

BMC Cancer

Research Article

John R. Stevens¹  Roger K. Wolff²  Martha L. Slattery²  Jennifer S. Herrick² 

[1] Department of Mathematics and Statistics, Utah State University, Logan, USA;Division of Epidemiology, Department of Internal Medicine, University of Utah, Logan, USA;

关键词: microRNA;    Colorectal cancer;    Epigenetics;    Differential expression;   

DOI  :  10.1186/s12885-017-3690-x

 received in 2017-02-01, accepted in 2017-10-16,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundmicroRNAs 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.MethodsUsing 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.ResultsWe 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.ConclusionsThe 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.

【 授权许可】

CC BY   
© The Author(s). 2017