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Whole Body Melanoma Transcriptome Response in Medaka
The incidence of malignant melanoma continues to increase each year with poor prognosis for survival in many relapse cases. To reverse this trend, whole body response measures are needed to discover collaborative paths to primary and secondary malignancy. Several species of fish provide excellent me...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4699850/ https://www.ncbi.nlm.nih.gov/pubmed/26714172 http://dx.doi.org/10.1371/journal.pone.0143057 |
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author | Schartl, Manfred Shen, Yingjia Maurus, Katja Walter, Ron Tomlinson, Chad Wilson, Richard K. Postlethwait, John Warren, Wesley C. |
author_facet | Schartl, Manfred Shen, Yingjia Maurus, Katja Walter, Ron Tomlinson, Chad Wilson, Richard K. Postlethwait, John Warren, Wesley C. |
author_sort | Schartl, Manfred |
collection | PubMed |
description | The incidence of malignant melanoma continues to increase each year with poor prognosis for survival in many relapse cases. To reverse this trend, whole body response measures are needed to discover collaborative paths to primary and secondary malignancy. Several species of fish provide excellent melanoma models because fish and human melanocytes both appear in the epidermis, and fish and human pigment cell tumors share conserved gene expression signatures. For the first time, we have examined the whole body transcriptome response to invasive melanoma as a prelude to using transcriptome profiling to screen for drugs in a medaka (Oryzias latipes) model. We generated RNA-seq data from whole body RNA isolates for controls and melanoma fish. After testing for differential expression, 396 genes had significantly different expression (adjusted p-value <0.02) in the whole body transcriptome between melanoma and control fish; 379 of these genes were matched to human orthologs with 233 having annotated human gene symbols and 14 matched genes that contain putative deleterious variants in human melanoma at varying levels of recurrence. A detailed canonical pathway evaluation for significant enrichment showed the top scoring pathway to be antigen presentation but also included the expected melanocyte development and pigmentation signaling pathway. Results revealed a profound down-regulation of genes involved in the immune response, especially the innate immune system. We hypothesize that the developing melanoma actively suppresses the immune system responses of the body in reacting to the invasive malignancy, and that this mal-adaptive response contributes to disease progression, a result that suggests our whole-body transcriptomic approach merits further use. In these findings, we also observed novel genes not yet identified in human melanoma expression studies and uncovered known and new candidate drug targets for further testing in this malignant melanoma medaka model. |
format | Online Article Text |
id | pubmed-4699850 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-46998502016-01-14 Whole Body Melanoma Transcriptome Response in Medaka Schartl, Manfred Shen, Yingjia Maurus, Katja Walter, Ron Tomlinson, Chad Wilson, Richard K. Postlethwait, John Warren, Wesley C. PLoS One Research Article The incidence of malignant melanoma continues to increase each year with poor prognosis for survival in many relapse cases. To reverse this trend, whole body response measures are needed to discover collaborative paths to primary and secondary malignancy. Several species of fish provide excellent melanoma models because fish and human melanocytes both appear in the epidermis, and fish and human pigment cell tumors share conserved gene expression signatures. For the first time, we have examined the whole body transcriptome response to invasive melanoma as a prelude to using transcriptome profiling to screen for drugs in a medaka (Oryzias latipes) model. We generated RNA-seq data from whole body RNA isolates for controls and melanoma fish. After testing for differential expression, 396 genes had significantly different expression (adjusted p-value <0.02) in the whole body transcriptome between melanoma and control fish; 379 of these genes were matched to human orthologs with 233 having annotated human gene symbols and 14 matched genes that contain putative deleterious variants in human melanoma at varying levels of recurrence. A detailed canonical pathway evaluation for significant enrichment showed the top scoring pathway to be antigen presentation but also included the expected melanocyte development and pigmentation signaling pathway. Results revealed a profound down-regulation of genes involved in the immune response, especially the innate immune system. We hypothesize that the developing melanoma actively suppresses the immune system responses of the body in reacting to the invasive malignancy, and that this mal-adaptive response contributes to disease progression, a result that suggests our whole-body transcriptomic approach merits further use. In these findings, we also observed novel genes not yet identified in human melanoma expression studies and uncovered known and new candidate drug targets for further testing in this malignant melanoma medaka model. Public Library of Science 2015-12-29 /pmc/articles/PMC4699850/ /pubmed/26714172 http://dx.doi.org/10.1371/journal.pone.0143057 Text en © 2015 Schartl et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Schartl, Manfred Shen, Yingjia Maurus, Katja Walter, Ron Tomlinson, Chad Wilson, Richard K. Postlethwait, John Warren, Wesley C. Whole Body Melanoma Transcriptome Response in Medaka |
title | Whole Body Melanoma Transcriptome Response in Medaka |
title_full | Whole Body Melanoma Transcriptome Response in Medaka |
title_fullStr | Whole Body Melanoma Transcriptome Response in Medaka |
title_full_unstemmed | Whole Body Melanoma Transcriptome Response in Medaka |
title_short | Whole Body Melanoma Transcriptome Response in Medaka |
title_sort | whole body melanoma transcriptome response in medaka |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4699850/ https://www.ncbi.nlm.nih.gov/pubmed/26714172 http://dx.doi.org/10.1371/journal.pone.0143057 |
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