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Metastasis-associated microRNA expression in canine uveal melanoma
M P Starkey1, L Compston-Garnett1, P Malho2
1Molecular Oncology Group, Animal Health Trust, Newmarket, UK.
Background:
Uveal melanoma (UM) is the most common primary intraocular tumour in dogs. There is no effective means of predicting whether a tumour will metastasize. microRNA (miRNA) metastasis signatures have been identified for several human cancers, including UM.
Aims:
In this study we investigated whether metastasizing and non-metastasizing canine UMs can be distinguished by miRNA expression levels.
Materials And Methods:
miRNA microarray profiling was used to compare miRNA expression in 8 metastasizing and 12 non-metastasizing formalin-fixed, paraffin-embedded (FFPE) primary UM biopsies.
Results:
Fourteen miRNAs exhibited statistically significant differences in expression between the metastasizing and non-metastasizing tumours. Class prediction analysis pinpointed 9 miRNAs which categorized tumours as metastasizing or non-metastasizing with an accuracy of 89%. Of the discriminating miRNAs, 8 were up-regulated in metastasizing UM, and included 3 miRNAs implicated as potential "metastasis activators" in human cutaneous melanoma. The expression of 4 of the miRNAs was subsequently measured using the quantitative reverse transcription polymerase chain reaction (RT-qPCR), and their up-regulation in metastasizing tumours validated.
Conclusion:
miRNA expression profiles may potentially be used to identify UMs that will metastasize, and miRNAs that are up-regulated in metastasizing tumours may be targets for therapeutic intervention.
