title: Whole Body Melanoma Transcriptome Response in Medaka.
abstract: 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.
authors.affiliation: Physiological Chemistry, University of Würzburg, Biozentrum, Am Hubland, 97074, Würzburg, Germany.|Comprehensive Cancer Center, University Clinic Würzburg, Josef Schneider Straße 6, 97074, Würzburg, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Schartl
authors.affiliation: Department of Chemistry and Biochemistry, 419 Centennial Hall, Texas State University, 601 University Drive, San Marcos, TX, 78666, United States of America.
authors.forename: Yingjia
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Physiological Chemistry, University of Würzburg, Biozentrum, Am Hubland, 97074, Würzburg, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Maurus
authors.affiliation: Department of Chemistry and Biochemistry, 419 Centennial Hall, Texas State University, 601 University Drive, San Marcos, TX, 78666, United States of America.
authors.forename: Ron
authors.initials: R
authors.lastname: Walter
authors.affiliation: McDonnell Genome Institute at Washington University, 4444 Forest Park Blvd., St Louis, MO, 63108, United States of America.
authors.forename: Chad
authors.initials: C
authors.lastname: Tomlinson
authors.affiliation: McDonnell Genome Institute at Washington University, 4444 Forest Park Blvd., St Louis, MO, 63108, United States of America.
authors.forename: Richard K
authors.initials: RK
authors.lastname: Wilson
authors.affiliation: Institute of Neuroscience, University of Oregon, 1425 E. 13th Avenue, Eugene, OR, 97403, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: Postlethwait
authors.affiliation: McDonnell Genome Institute at Washington University, 4444 Forest Park Blvd., St Louis, MO, 63108, United States of America.
authors.forename: Wesley C
authors.initials: WC
authors.lastname: Warren
mesh_terms: D000818:Animals; D029941:Fish Proteins / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D008544:Melanocytes / Q000378:metabolism; D008545:Melanoma / Q000235:genetics / Q000378:metabolism*; D009990:Oryzias / Q000235:genetics / Q000378:metabolism; D010858:Pigmentation / Q000235:genetics; D020543:Proteome / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: D029941:Fish Proteins; D020543:Proteome