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Prognostic significance of deregulated microRNAs in uveal melanomas

Uveal melanoma (UM) represents the most frequent primary tumor of the eye. Despite the development of new drugs and screening programs, the prognosis of patients with UM remains poor and no effective prognostic biomarkers are yet able to identify high-risk patients. Therefore, in the present study,...

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Autores principales: Falzone, Luca, Romano, Giovanni L., Salemi, Rossella, Bucolo, Claudio, Tomasello, Barbara, Lupo, Gabriella, Anfuso, Carmelina D., Spandidos, Demetrios A., Libra, Massimo, Candido, Saverio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423615/
https://www.ncbi.nlm.nih.gov/pubmed/30816460
http://dx.doi.org/10.3892/mmr.2019.9949
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author Falzone, Luca
Romano, Giovanni L.
Salemi, Rossella
Bucolo, Claudio
Tomasello, Barbara
Lupo, Gabriella
Anfuso, Carmelina D.
Spandidos, Demetrios A.
Libra, Massimo
Candido, Saverio
author_facet Falzone, Luca
Romano, Giovanni L.
Salemi, Rossella
Bucolo, Claudio
Tomasello, Barbara
Lupo, Gabriella
Anfuso, Carmelina D.
Spandidos, Demetrios A.
Libra, Massimo
Candido, Saverio
author_sort Falzone, Luca
collection PubMed
description Uveal melanoma (UM) represents the most frequent primary tumor of the eye. Despite the development of new drugs and screening programs, the prognosis of patients with UM remains poor and no effective prognostic biomarkers are yet able to identify high-risk patients. Therefore, in the present study, microRNA (miRNA or miR) expression data, contained in the TCGA UM (UVM) database, were analyzed in order to identify a set of miRNAs with prognostic significance to be used as biomarkers in clinical practice. Patients were stratified into 2 groups, including tumor stage (high-grade vs. low-grade) and status (deceased vs. alive); differential analyses of miRNA expression among these groups were performed. A total of 20 deregulated miRNAs for each group were identified. In total 7 miRNAs were common between the groups. The majority of common miRNAs belonged to the miR-506-514 cluster, known to be involved in UM development. The prognostic value of the 20 selected miRNAs related to tumor stage was assessed. The deregulation of 12 miRNAs (6 upregulated and 6 downregulated) was associated with a worse prognosis of patients with UM. Subsequently, miRCancerdb and microRNA Data Integration Portal bioinformatics tools were used to identify a set of genes associated with the 20 miRNAs and to establish their interaction levels. By this approach, 53 different negatively and positively associated genes were identified. Finally, DIANA-mirPath prediction pathway and Gene Ontology enrichment analyses were performed on the lists of genes previously generated to establish their functional involvement in biological processes and molecular pathways. All the miRNAs and genes were involved in molecular pathways usually altered in cancer, including the mitogen-activated protein kinase (MAPK) pathway. Overall, the findings of the presents study demonstrated that the miRNAs of the miR-506-514 cluster, hsa-miR-592 and hsa-miR-199a-5p were the most deregulated miRNAs in patients with high-grade disease compared to those with low-grade disease and were strictly related to the overall survival (OS) of the patients. However, further in vitro and translational approaches are required to validate these preliminary findings.
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spelling pubmed-64236152019-03-22 Prognostic significance of deregulated microRNAs in uveal melanomas Falzone, Luca Romano, Giovanni L. Salemi, Rossella Bucolo, Claudio Tomasello, Barbara Lupo, Gabriella Anfuso, Carmelina D. Spandidos, Demetrios A. Libra, Massimo Candido, Saverio Mol Med Rep Articles Uveal melanoma (UM) represents the most frequent primary tumor of the eye. Despite the development of new drugs and screening programs, the prognosis of patients with UM remains poor and no effective prognostic biomarkers are yet able to identify high-risk patients. Therefore, in the present study, microRNA (miRNA or miR) expression data, contained in the TCGA UM (UVM) database, were analyzed in order to identify a set of miRNAs with prognostic significance to be used as biomarkers in clinical practice. Patients were stratified into 2 groups, including tumor stage (high-grade vs. low-grade) and status (deceased vs. alive); differential analyses of miRNA expression among these groups were performed. A total of 20 deregulated miRNAs for each group were identified. In total 7 miRNAs were common between the groups. The majority of common miRNAs belonged to the miR-506-514 cluster, known to be involved in UM development. The prognostic value of the 20 selected miRNAs related to tumor stage was assessed. The deregulation of 12 miRNAs (6 upregulated and 6 downregulated) was associated with a worse prognosis of patients with UM. Subsequently, miRCancerdb and microRNA Data Integration Portal bioinformatics tools were used to identify a set of genes associated with the 20 miRNAs and to establish their interaction levels. By this approach, 53 different negatively and positively associated genes were identified. Finally, DIANA-mirPath prediction pathway and Gene Ontology enrichment analyses were performed on the lists of genes previously generated to establish their functional involvement in biological processes and molecular pathways. All the miRNAs and genes were involved in molecular pathways usually altered in cancer, including the mitogen-activated protein kinase (MAPK) pathway. Overall, the findings of the presents study demonstrated that the miRNAs of the miR-506-514 cluster, hsa-miR-592 and hsa-miR-199a-5p were the most deregulated miRNAs in patients with high-grade disease compared to those with low-grade disease and were strictly related to the overall survival (OS) of the patients. However, further in vitro and translational approaches are required to validate these preliminary findings. D.A. Spandidos 2019-04 2019-02-11 /pmc/articles/PMC6423615/ /pubmed/30816460 http://dx.doi.org/10.3892/mmr.2019.9949 Text en Copyright: © Falzone et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Falzone, Luca
Romano, Giovanni L.
Salemi, Rossella
Bucolo, Claudio
Tomasello, Barbara
Lupo, Gabriella
Anfuso, Carmelina D.
Spandidos, Demetrios A.
Libra, Massimo
Candido, Saverio
Prognostic significance of deregulated microRNAs in uveal melanomas
title Prognostic significance of deregulated microRNAs in uveal melanomas
title_full Prognostic significance of deregulated microRNAs in uveal melanomas
title_fullStr Prognostic significance of deregulated microRNAs in uveal melanomas
title_full_unstemmed Prognostic significance of deregulated microRNAs in uveal melanomas
title_short Prognostic significance of deregulated microRNAs in uveal melanomas
title_sort prognostic significance of deregulated micrornas in uveal melanomas
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423615/
https://www.ncbi.nlm.nih.gov/pubmed/30816460
http://dx.doi.org/10.3892/mmr.2019.9949
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