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...

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Main Authors: Manfred Schartl, Yingjia Shen, Katja Maurus, Ron Walter, Chad Tomlinson, Richard K Wilson, John Postlethwait, Wesley C Warren
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4699850?pdf=render
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spelling doaj-f51e3a85a69e4ca88a85791d134649c92020-11-25T01:30:47ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011012e014305710.1371/journal.pone.0143057Whole Body Melanoma Transcriptome Response in Medaka.Manfred SchartlYingjia ShenKatja MaurusRon WalterChad TomlinsonRichard K WilsonJohn PostlethwaitWesley C WarrenThe 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.http://europepmc.org/articles/PMC4699850?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Manfred Schartl
Yingjia Shen
Katja Maurus
Ron Walter
Chad Tomlinson
Richard K Wilson
John Postlethwait
Wesley C Warren
spellingShingle Manfred Schartl
Yingjia Shen
Katja Maurus
Ron Walter
Chad Tomlinson
Richard K Wilson
John Postlethwait
Wesley C Warren
Whole Body Melanoma Transcriptome Response in Medaka.
PLoS ONE
author_facet Manfred Schartl
Yingjia Shen
Katja Maurus
Ron Walter
Chad Tomlinson
Richard K Wilson
John Postlethwait
Wesley C Warren
author_sort Manfred Schartl
title Whole Body Melanoma Transcriptome Response in Medaka.
title_short 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_sort whole body melanoma transcriptome response in medaka.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2015-01-01
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.
url http://europepmc.org/articles/PMC4699850?pdf=render
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