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Metastasis‐associated microRNA expression in canine uveal melanoma
Author(s) -
Starkey M. P.,
CompstonGarnett L.,
Malho P.,
Dunn K.,
Dubielzig R.
Publication year - 2018
Publication title -
veterinary and comparative oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 34
eISSN - 1476-5829
pISSN - 1476-5810
DOI - 10.1111/vco.12315
Subject(s) - microrna , melanoma , metastasis , reverse transcription polymerase chain reaction , gene expression profiling , microarray , cancer research , pathology , biology , real time polymerase chain reaction , medicine , gene expression , cancer , gene , genetics
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.