miRNA Expression Profiles Predict Metastatic Risk in Uveal Melanoma
miRNA Expression Profiles Predict Metastatic Risk in Uveal Melanoma
A review of miRNAs associated with metastasis in uveal melanoma identified by multiplexed microarray profiling
Note: This is a review of the published article listed below. All information, quotes, figures, methods, and findings mentioned in this review are from that article, and are the property of its authors and/or the publication in which the article originally appeared.
To better understand the relationship between melanoma metastasis and microRNAs (miRNAs), the small non-coding RNAs that regulate gene expression, researchers at Washington University analyzed the miRNA profiles of primary uveal (eye) melanomas. They studied a tumor set that was the focus of their earlier work which identified gene expression signatures associated with the two prognostically significant subtypes of uveal melanoma: class 1 (low metastatic risk) and class 2 (high metastatic risk). The miRNA expression profiles were obtained using Agilent Human miRNA microarrays (version 1.0) and features were extracted using Agilent FE software. Unsupervised analysis using principle component analysis (PCA) of the miRNA microarray data separated the tumors into two groups that correspond to the same subtypes identified by gene expression profiling (Figure 1). Only the first two components of the PCA plot were required to classify the tumors as class 1 or class 2. A comparison of the miRNA expression levels between class 1 and class 2 tumors revealed that 68 miRNAs were upregulated in class 1 tumors and six miRNAs were upregulated in class 2 tumors (Figure 2). Supervised analysis identified six differentially expressed miRNAs that strongly discriminate tumor class— the same six miRNAs identified by PCA.
The researchers compared the quality of discrimination between the tumor classes using all six of the differentially expressed miRNAs or using only the two miRNAs with the strongest correlation to endpoints that identify uveal melanoma biomarkers. Inclusion of all six miRNAs resulted in better discrimination which suggests that each miRNA adds independent information to the class prediction (Figure 3).
All six of the discriminating miRNAs were upregulated in class 2 tumors, an intriguing finding since the group’s earlier studies showed that the most discriminating mRNAs are downregulated in class 2 tumors. The researchers propose that the abundance of down-regulated mRNA discriminators in aggressive tumors may be the result of up- regulation of miRNAs in these tumors.
Figure 1. Unsupervised PCA of miRNA profiles in primary uveal melanomas. Two-dimensional PCA, created by display of the first two principal components, showing that class 1 tumors (blue circles) and class 2 tumors (red circles) segregate into distinct clusters based on miRNA expression patterns.
Figure 2. Plot of mean miRNA expression in class 1 versus class 2 tumors. Spheres represent individual miRNAs. Diagonal lines demarcate two-fold difference levels in expression between class 1 and class 2 tumors. The six miRNAs that were upregulated greater than two-fold in class 2 tumors are indicated in red, whereas those that were downregulated greater than two-fold are indicated in blue.
Figure 3. Significance analysis of microarray (SAM) plot showing differentially expressed miRNAs. Most miRNAs were not significant discriminators of class (gray circles), except for six miRNAs that were all significant and all upregulated in the class two tumors (white circles). miRNA, micro-RNA.
Adapted by permission from Lippincott Williams & Wilkins: Melanoma Research 18:184-190, 2008.
Title: Micro-RNAs associated with metastasis in uveal melanoma identified by multiplexed microarray profiling.
Authors: Lori A. Worley, Meghan D. Long, Michael D. Onken and J. William Harbour.
Journal: Melanoma Research. 2008 18:184-190.
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