Global gene expression analysis of canine cutaneous mast cell tumor: could molecular profiling be useful for subtype classification and prognostication?

Prognosis and therapeutic management of dogs with cutaneous mast cell tumors (MCTs) depend on clinical stage and histological grade. However, the prognostic value of this latter is still questionable. In the present study, MCT transcriptome was analyzed to identify a set of candidate genes potential...

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Autores principales:	Mery Giantin, Anna Granato, Chiara Baratto, Laura Marconato, Marta Vascellari, Emanuela M Morello, Antonella Vercelli, Franco Mutinelli, Mauro Dacasto
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9a871f67b9934c63ae363682d587e174
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spelling	oai:doaj.org-article:9a871f67b9934c63ae363682d587e1742021-11-18T08:22:24ZGlobal gene expression analysis of canine cutaneous mast cell tumor: could molecular profiling be useful for subtype classification and prognostication?1932-620310.1371/journal.pone.0095481https://doaj.org/article/9a871f67b9934c63ae363682d587e1742014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24748173/?tool=EBIhttps://doaj.org/toc/1932-6203Prognosis and therapeutic management of dogs with cutaneous mast cell tumors (MCTs) depend on clinical stage and histological grade. However, the prognostic value of this latter is still questionable. In the present study, MCT transcriptome was analyzed to identify a set of candidate genes potentially useful for predicting the biological behavior of MCTs. Fifty-one canine MCT biopsies were analyzed. Isolated and purified total RNAs were individually hybridized to the Agilent Canine V2 4x44k DNA microarray. The comparison of reference differentiated and undifferentiated MCT transcriptome revealed a total of 597 differentially expressed genes (147 down-regulated and 450 up-regulated). The functional analysis of this set of genes provided evidence that they were mainly involved in cell cycle, DNA replication, p53 signaling pathway, nucleotide excision repair and pyrimidine metabolism. Class prediction analysis identified 13 transcripts providing the greatest accuracy of class prediction and divided samples into two categories (differentiated and undifferentiated), harboring a different prognosis. The Principal Component Analysis of all samples, made by using the selected 13 markers, confirmed MCT classification. The first three components accounted for 99.924% of the total variance. This molecular classification significantly correlated with survival time (p = 0.0026). Furthermore, among all marker genes, a significant association was found between mRNA expression and MCT-related mortality for FOXM1, GSN, FEN1 and KPNA2 (p<0.05). Finally, marker genes mRNA expression was evaluated in a cohort of 22 independent samples. Data obtained enabled to identify MCT cases with different prognosis. Overall, the molecular characterization of canine MCT transcriptome allowed the identification of a set of 13 transcripts that clearly separated differentiated from undifferentiated MCTs, thus predicting outcome regardless of the histological grade. These results may have clinical relevance and warrant future validation in a prospective study.Mery GiantinAnna GranatoChiara BarattoLaura MarconatoMarta VascellariEmanuela M MorelloAntonella VercelliFranco MutinelliMauro DacastoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 4, p e95481 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mery Giantin Anna Granato Chiara Baratto Laura Marconato Marta Vascellari Emanuela M Morello Antonella Vercelli Franco Mutinelli Mauro Dacasto Global gene expression analysis of canine cutaneous mast cell tumor: could molecular profiling be useful for subtype classification and prognostication?
description	Prognosis and therapeutic management of dogs with cutaneous mast cell tumors (MCTs) depend on clinical stage and histological grade. However, the prognostic value of this latter is still questionable. In the present study, MCT transcriptome was analyzed to identify a set of candidate genes potentially useful for predicting the biological behavior of MCTs. Fifty-one canine MCT biopsies were analyzed. Isolated and purified total RNAs were individually hybridized to the Agilent Canine V2 4x44k DNA microarray. The comparison of reference differentiated and undifferentiated MCT transcriptome revealed a total of 597 differentially expressed genes (147 down-regulated and 450 up-regulated). The functional analysis of this set of genes provided evidence that they were mainly involved in cell cycle, DNA replication, p53 signaling pathway, nucleotide excision repair and pyrimidine metabolism. Class prediction analysis identified 13 transcripts providing the greatest accuracy of class prediction and divided samples into two categories (differentiated and undifferentiated), harboring a different prognosis. The Principal Component Analysis of all samples, made by using the selected 13 markers, confirmed MCT classification. The first three components accounted for 99.924% of the total variance. This molecular classification significantly correlated with survival time (p = 0.0026). Furthermore, among all marker genes, a significant association was found between mRNA expression and MCT-related mortality for FOXM1, GSN, FEN1 and KPNA2 (p<0.05). Finally, marker genes mRNA expression was evaluated in a cohort of 22 independent samples. Data obtained enabled to identify MCT cases with different prognosis. Overall, the molecular characterization of canine MCT transcriptome allowed the identification of a set of 13 transcripts that clearly separated differentiated from undifferentiated MCTs, thus predicting outcome regardless of the histological grade. These results may have clinical relevance and warrant future validation in a prospective study.
format	article
author	Mery Giantin Anna Granato Chiara Baratto Laura Marconato Marta Vascellari Emanuela M Morello Antonella Vercelli Franco Mutinelli Mauro Dacasto
author_facet	Mery Giantin Anna Granato Chiara Baratto Laura Marconato Marta Vascellari Emanuela M Morello Antonella Vercelli Franco Mutinelli Mauro Dacasto
author_sort	Mery Giantin
title	Global gene expression analysis of canine cutaneous mast cell tumor: could molecular profiling be useful for subtype classification and prognostication?
title_short	Global gene expression analysis of canine cutaneous mast cell tumor: could molecular profiling be useful for subtype classification and prognostication?
title_full	Global gene expression analysis of canine cutaneous mast cell tumor: could molecular profiling be useful for subtype classification and prognostication?
title_fullStr	Global gene expression analysis of canine cutaneous mast cell tumor: could molecular profiling be useful for subtype classification and prognostication?
title_full_unstemmed	Global gene expression analysis of canine cutaneous mast cell tumor: could molecular profiling be useful for subtype classification and prognostication?
title_sort	global gene expression analysis of canine cutaneous mast cell tumor: could molecular profiling be useful for subtype classification and prognostication?
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/9a871f67b9934c63ae363682d587e174
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Global gene expression analysis of canine cutaneous mast cell tumor: could molecular profiling be useful for subtype classification and prognostication?

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