The use of miRNA microarrays for the analysis of cancer samples with global miRNA decrease
Details
Publication Year 2013-07, Volume 19, Issue #7, Page 876-888
Journal Title
RNA-A PUBLICATION OF THE RNA SOCIETY
Publication Type
Journal Article
Abstract
Recent studies have established that mutations or deletions in microRNA(miRNA) processing enzymes resulting in a global decrease of miRNA expression are frequent across cancers and can be associated with a poorer prognosis. While very popular in miRNA profiling studies, it remains unclear whether miRNA microarrays are suited or not to accurately detecting global miRNA decreases seen in cancers. In this work, we analyzed the miRNA profiles of samples with global miRNA decreases using Affymetrix miRNA microarrays following the inducible genetic deletion of Dicer1. Surprisingly, up to a third of deregulated miRNAs identified upon Dicer1 depletion were found to be up-regulated following standard robust multichip average (RMA) background correction and quantile normalization, indicative of normalization bias. Our comparisons of five preprocess steps performed at the probe level demonstrated that the use of cyclic loess relying on non-miRNA small RNAs present on the Affymetrix platform significantly improved specificity and sensitivity of detection of decreased miRNAs. These findings were validated in samples from patients with prostate cancer, where conjugation of robust normal-exponential background correction with cyclic loess normalization and array weights correctly identified the greatest number of decreased miRNAs, and the lowest amount of false-positive up-regulated miRNAs. These findings highlight the importance of miRNA microarray normalization for the detection of miRNAs that are truly differentially expressed and suggest that the use of cyclic loess based on non-miRNA small RNAs can help to improve the sensitivity and specificity of miRNA profiling in cancer samples with global miRNA decrease.
Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
Keywords
microRNA ; miRNA microarray ; normalization ; Dicer1
WEHI Research Division(s)
Bioinformatics
Rights Notice
© 2013; Published by Cold Spring Harbor Laboratory Press for the RNA Society


Creation Date: 2013-07-01 12:00:00
Last Modified: 0001-01-01 12:00:00
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