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Prognostic value of epigenetic markers for canine mast cell cancer

Canine Mast cell tumors (MCTs) constitute approximately 21% of all canine skin tumors. Despite the use of comprehensive grading systems, biological aggressiveness is sometimes difficult to predict, therefore there is a need for better prognostic markers. Progression in various cancers involves DNA h...

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Autores principales: Syed, Shahzar, Knight, Britta J., Wood, Geoffrey A., Coomber, Brenda Lynn
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10062589/
https://www.ncbi.nlm.nih.gov/pubmed/36996057
http://dx.doi.org/10.1371/journal.pone.0283616
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author Syed, Shahzar
Knight, Britta J.
Wood, Geoffrey A.
Coomber, Brenda Lynn
author_facet Syed, Shahzar
Knight, Britta J.
Wood, Geoffrey A.
Coomber, Brenda Lynn
author_sort Syed, Shahzar
collection PubMed
description Canine Mast cell tumors (MCTs) constitute approximately 21% of all canine skin tumors. Despite the use of comprehensive grading systems, biological aggressiveness is sometimes difficult to predict, therefore there is a need for better prognostic markers. Progression in various cancers involves DNA hypermethylation, hypomethylation and epigenetic enzyme dysregulation. Therefore, global levels of 5-methylcytosine, 5-hydroxymethylcytosine and associated enzymes DNMT1, and IDH1 expression may predict MCT aggressiveness. A tissue microarray (TMA) with cores from 244 different tumor samples from 189 dogs was immunolabelled and used to quantify the global DNA methylation and hydroxymethylation levels as well as the levels of the enzymes involved in DNA methylation and their relationship with canine MCT outcome. From the immunolabelled TMA, H-scores were generated using QuPath (v0.1.2) and analyzed with associated patient data. High 5MC and DNMT1, and low IDH1 levels were associated with poorer outcome when looking at all canine MCT cases. High 5MC levels showed significance for shorter disease-free interval (DFI) in subcutaneous cases and high 5MC levels showed poorer DFI and overall survival (OS) in cases with Kiupel’s grading system high grade. Cases with grade II in Patnaik’s grading system showed better DFI with low levels of DNMT1 and better OS with low levels of 5MC and 5HMC. High levels of DNMT1 staining were also associated with shorter DFI for dermal MCTs. For cases that received adjuvant therapy in addition to surgery, all parameters except IDH1 were significantly associated with OS. Therefore, there is potential for DNA methylation status and levels of enzymes associated with DNA methylation pathways to better predict outcome in canine MCT, and to possibly influence treatment decisions.
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spelling pubmed-100625892023-03-31 Prognostic value of epigenetic markers for canine mast cell cancer Syed, Shahzar Knight, Britta J. Wood, Geoffrey A. Coomber, Brenda Lynn PLoS One Research Article Canine Mast cell tumors (MCTs) constitute approximately 21% of all canine skin tumors. Despite the use of comprehensive grading systems, biological aggressiveness is sometimes difficult to predict, therefore there is a need for better prognostic markers. Progression in various cancers involves DNA hypermethylation, hypomethylation and epigenetic enzyme dysregulation. Therefore, global levels of 5-methylcytosine, 5-hydroxymethylcytosine and associated enzymes DNMT1, and IDH1 expression may predict MCT aggressiveness. A tissue microarray (TMA) with cores from 244 different tumor samples from 189 dogs was immunolabelled and used to quantify the global DNA methylation and hydroxymethylation levels as well as the levels of the enzymes involved in DNA methylation and their relationship with canine MCT outcome. From the immunolabelled TMA, H-scores were generated using QuPath (v0.1.2) and analyzed with associated patient data. High 5MC and DNMT1, and low IDH1 levels were associated with poorer outcome when looking at all canine MCT cases. High 5MC levels showed significance for shorter disease-free interval (DFI) in subcutaneous cases and high 5MC levels showed poorer DFI and overall survival (OS) in cases with Kiupel’s grading system high grade. Cases with grade II in Patnaik’s grading system showed better DFI with low levels of DNMT1 and better OS with low levels of 5MC and 5HMC. High levels of DNMT1 staining were also associated with shorter DFI for dermal MCTs. For cases that received adjuvant therapy in addition to surgery, all parameters except IDH1 were significantly associated with OS. Therefore, there is potential for DNA methylation status and levels of enzymes associated with DNA methylation pathways to better predict outcome in canine MCT, and to possibly influence treatment decisions. Public Library of Science 2023-03-30 /pmc/articles/PMC10062589/ /pubmed/36996057 http://dx.doi.org/10.1371/journal.pone.0283616 Text en © 2023 Syed et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Syed, Shahzar
Knight, Britta J.
Wood, Geoffrey A.
Coomber, Brenda Lynn
Prognostic value of epigenetic markers for canine mast cell cancer
title Prognostic value of epigenetic markers for canine mast cell cancer
title_full Prognostic value of epigenetic markers for canine mast cell cancer
title_fullStr Prognostic value of epigenetic markers for canine mast cell cancer
title_full_unstemmed Prognostic value of epigenetic markers for canine mast cell cancer
title_short Prognostic value of epigenetic markers for canine mast cell cancer
title_sort prognostic value of epigenetic markers for canine mast cell cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10062589/
https://www.ncbi.nlm.nih.gov/pubmed/36996057
http://dx.doi.org/10.1371/journal.pone.0283616
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