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Lauge Hjorth Mikkelsen, Ann-Cathrine Larsen, Peter Toft, Karin Wadt, Mette Klarskov Andersen, Steffen Heegaard; MiRNA expression in conjunctival melanoma and their pair-matched metastasis. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3188. doi: https://doi.org/.
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Purpose: To investigate the miRNA expression in primary conjunctival melanoma and their pair-matched metastasis.
13 patients with metastatic conjunctival melanoma were identified. Paraffin embedded tissue was retrieved from the primary tumors along with the distant metastasis. 29 conjunctival melanoma without metastasis were used as reference. Normal conjunctival tissue was used as control. Microarray analysis was performed using an Affymetrix 4.1 microarray. The data was analyzed with unsupervised clustering analysis using a GEE model. Differentially expressed miRNAs were defined as a miRNA demonstrating a Fold change >2 and false discovery rate <0.1. A functional KEGG pathway analysis was performed using the DIANA mirpath 3.0 tool.
22 miRNAs were found to be differentially expressed when comparing primary conjunctival melanoma and their coupled metastasis. 12 miRNAs were upregulated and 10 were downregulated. Primary tumor and metastasis clustered separately except two cases where the metastasis and the primary tumor clustered together. The KEGG analysis showed that the functional pathways affected in the metastasis included fatty acid biosynthesis, spliceosome, and cell adhesion.When comparing the primary tumors and the controls, 24 miRNAS were differentially expressed. 21 were upregulated and 3 were downregulated. None of the identified miRNAS have previously been identified in conjunctival melanoma.
We identified 22 miRNAs differentially expressed in primary conjunctival melanoma and their pair-matched metastasis. None of these have previously been identified in conjunctival melanoma. A functional KEGG analysis revealed that pathways involved in cell adhesion, spliceosome, and fatty acid biosynthesis were affected in the metastasis. Our results provide new insight into the processes leading to metastasis in conjunctival melanoma. The identification of these differentially expressed miRNAs provides an entry point for future functional studies of miRNAs as prognostic or therapeutic targets in CM
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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