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Transcriptional characterization of conjunctival melanoma identifies the cellular tumor microenvironment and prognostic gene signatures
This study characterizes the transcriptome and the cellular tumor microenvironment (TME) of conjunctival melanoma (CM) and identifies prognostically relevant biomarkers. 12 formalin-fixed and paraffin-embedded CM were analyzed by MACE RNA sequencing, including six cases each with good or poor clinic...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550331/ https://www.ncbi.nlm.nih.gov/pubmed/33046735 http://dx.doi.org/10.1038/s41598-020-72864-0 |
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author | Wolf, Julian Auw-Haedrich, Claudia Schlecht, Anja Boneva, Stefaniya Mittelviefhaus, Hans Lapp, Thabo Agostini, Hansjürgen Reinhard, Thomas Schlunck, Günther Lange, Clemens A. K. |
author_facet | Wolf, Julian Auw-Haedrich, Claudia Schlecht, Anja Boneva, Stefaniya Mittelviefhaus, Hans Lapp, Thabo Agostini, Hansjürgen Reinhard, Thomas Schlunck, Günther Lange, Clemens A. K. |
author_sort | Wolf, Julian |
collection | PubMed |
description | This study characterizes the transcriptome and the cellular tumor microenvironment (TME) of conjunctival melanoma (CM) and identifies prognostically relevant biomarkers. 12 formalin-fixed and paraffin-embedded CM were analyzed by MACE RNA sequencing, including six cases each with good or poor clinical outcome, the latter being defined by local recurrence and/or systemic metastases. Eight healthy conjunctival specimens served as controls. The TME of CM, as determined by bioinformatic cell type enrichment analysis, was characterized by the enrichment of melanocytes, pericytes and especially various immune cell types, such as plasmacytoid dendritic cells, natural killer T cells, B cells and mast cells. Differentially expressed genes between CM and control were mainly involved in inhibition of apoptosis, proteolysis and response to growth factors. POU3F3, BIRC5 and 7 were among the top expressed genes associated with inhibition of apoptosis. 20 genes, among them CENPK, INHA, USP33, CASP3, SNORA73B, AAR2, SNRNP48 and GPN1, were identified as prognostically relevant factors reaching high classification accuracy (area under the curve: 1.0). The present study provides new insights into the TME and the transcriptional profile of CM and additionally identifies new prognostic biomarkers. These results add new diagnostic tools and may lead to new options of targeted therapy for CM. |
format | Online Article Text |
id | pubmed-7550331 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-75503312020-10-14 Transcriptional characterization of conjunctival melanoma identifies the cellular tumor microenvironment and prognostic gene signatures Wolf, Julian Auw-Haedrich, Claudia Schlecht, Anja Boneva, Stefaniya Mittelviefhaus, Hans Lapp, Thabo Agostini, Hansjürgen Reinhard, Thomas Schlunck, Günther Lange, Clemens A. K. Sci Rep Article This study characterizes the transcriptome and the cellular tumor microenvironment (TME) of conjunctival melanoma (CM) and identifies prognostically relevant biomarkers. 12 formalin-fixed and paraffin-embedded CM were analyzed by MACE RNA sequencing, including six cases each with good or poor clinical outcome, the latter being defined by local recurrence and/or systemic metastases. Eight healthy conjunctival specimens served as controls. The TME of CM, as determined by bioinformatic cell type enrichment analysis, was characterized by the enrichment of melanocytes, pericytes and especially various immune cell types, such as plasmacytoid dendritic cells, natural killer T cells, B cells and mast cells. Differentially expressed genes between CM and control were mainly involved in inhibition of apoptosis, proteolysis and response to growth factors. POU3F3, BIRC5 and 7 were among the top expressed genes associated with inhibition of apoptosis. 20 genes, among them CENPK, INHA, USP33, CASP3, SNORA73B, AAR2, SNRNP48 and GPN1, were identified as prognostically relevant factors reaching high classification accuracy (area under the curve: 1.0). The present study provides new insights into the TME and the transcriptional profile of CM and additionally identifies new prognostic biomarkers. These results add new diagnostic tools and may lead to new options of targeted therapy for CM. Nature Publishing Group UK 2020-10-12 /pmc/articles/PMC7550331/ /pubmed/33046735 http://dx.doi.org/10.1038/s41598-020-72864-0 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Wolf, Julian Auw-Haedrich, Claudia Schlecht, Anja Boneva, Stefaniya Mittelviefhaus, Hans Lapp, Thabo Agostini, Hansjürgen Reinhard, Thomas Schlunck, Günther Lange, Clemens A. K. Transcriptional characterization of conjunctival melanoma identifies the cellular tumor microenvironment and prognostic gene signatures |
title | Transcriptional characterization of conjunctival melanoma identifies the cellular tumor microenvironment and prognostic gene signatures |
title_full | Transcriptional characterization of conjunctival melanoma identifies the cellular tumor microenvironment and prognostic gene signatures |
title_fullStr | Transcriptional characterization of conjunctival melanoma identifies the cellular tumor microenvironment and prognostic gene signatures |
title_full_unstemmed | Transcriptional characterization of conjunctival melanoma identifies the cellular tumor microenvironment and prognostic gene signatures |
title_short | Transcriptional characterization of conjunctival melanoma identifies the cellular tumor microenvironment and prognostic gene signatures |
title_sort | transcriptional characterization of conjunctival melanoma identifies the cellular tumor microenvironment and prognostic gene signatures |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550331/ https://www.ncbi.nlm.nih.gov/pubmed/33046735 http://dx.doi.org/10.1038/s41598-020-72864-0 |
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