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Additive Role of Immune System Infiltration and Angiogenesis in Uveal Melanoma Progression

Uveal melanoma (UM) is a malignant tumor that arises in the melanocytes of the uveal tract. It is the most frequent eye cancer, and despite new therapeutic approaches, prognosis is still poor, with up to 50% of patients developing metastasis with no efficient treatment options available. In contrast...

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Autores principales: García-Mulero, Sandra, Alonso, Maria Henar, del Carpio, Luis P., Sanz-Pamplona, Rebeca, Piulats, Josep M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961481/
https://www.ncbi.nlm.nih.gov/pubmed/33800878
http://dx.doi.org/10.3390/ijms22052669
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author García-Mulero, Sandra
Alonso, Maria Henar
del Carpio, Luis P.
Sanz-Pamplona, Rebeca
Piulats, Josep M.
author_facet García-Mulero, Sandra
Alonso, Maria Henar
del Carpio, Luis P.
Sanz-Pamplona, Rebeca
Piulats, Josep M.
author_sort García-Mulero, Sandra
collection PubMed
description Uveal melanoma (UM) is a malignant tumor that arises in the melanocytes of the uveal tract. It is the most frequent eye cancer, and despite new therapeutic approaches, prognosis is still poor, with up to 50% of patients developing metastasis with no efficient treatment options available. In contrast to cutaneous melanoma, UM is considered an “immune-cold” tumor due to the low mutational burden and the unique immunosuppressive microenvironment. To gain insight into the role of the UM microenvironment in regard to prognosis and metastatic progression, we have performed a pool analysis characterizing the UM microenvironment by using a bioinformatic approach. A variety of scores based on gene expression measuring stromal infiltration were calculated and used to assess association with prognosis. As a result, the highest immune and stromal scores were associated with poor prognosis. Specifically, stromal cells (fibroblasts and endothelial cells), T cells CD8+, natural killer (NK) cells, and macrophages M1 and M2 infiltration were associated with poor prognosis. Contrary to other tumors, lymphocytic infiltration is related to poor prognosis. Only B cells were associated with more favorable prognosis. UM samples scoring high in both angiogenesis (Angio) and antigen presentation (AP) pathways showed a poor prognosis suggesting an additive role of both functions. Almost all these tumors exhibited a chromosome 3 monosomy. Finally, an enrichment analysis showed that tumors classified as high Angio-high AP also activated metabolic pathways such as glycolysis or PI3K-AKT-MTOR. In summary, our pool analysis identified a cluster of samples with angiogenic and inflammatory phenotypes exhibiting poor prognosis and metabolic activation. Our analysis showed robust results replicated in a pool analysis merging different datasets from different analytic platforms.
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spelling pubmed-79614812021-03-17 Additive Role of Immune System Infiltration and Angiogenesis in Uveal Melanoma Progression García-Mulero, Sandra Alonso, Maria Henar del Carpio, Luis P. Sanz-Pamplona, Rebeca Piulats, Josep M. Int J Mol Sci Article Uveal melanoma (UM) is a malignant tumor that arises in the melanocytes of the uveal tract. It is the most frequent eye cancer, and despite new therapeutic approaches, prognosis is still poor, with up to 50% of patients developing metastasis with no efficient treatment options available. In contrast to cutaneous melanoma, UM is considered an “immune-cold” tumor due to the low mutational burden and the unique immunosuppressive microenvironment. To gain insight into the role of the UM microenvironment in regard to prognosis and metastatic progression, we have performed a pool analysis characterizing the UM microenvironment by using a bioinformatic approach. A variety of scores based on gene expression measuring stromal infiltration were calculated and used to assess association with prognosis. As a result, the highest immune and stromal scores were associated with poor prognosis. Specifically, stromal cells (fibroblasts and endothelial cells), T cells CD8+, natural killer (NK) cells, and macrophages M1 and M2 infiltration were associated with poor prognosis. Contrary to other tumors, lymphocytic infiltration is related to poor prognosis. Only B cells were associated with more favorable prognosis. UM samples scoring high in both angiogenesis (Angio) and antigen presentation (AP) pathways showed a poor prognosis suggesting an additive role of both functions. Almost all these tumors exhibited a chromosome 3 monosomy. Finally, an enrichment analysis showed that tumors classified as high Angio-high AP also activated metabolic pathways such as glycolysis or PI3K-AKT-MTOR. In summary, our pool analysis identified a cluster of samples with angiogenic and inflammatory phenotypes exhibiting poor prognosis and metabolic activation. Our analysis showed robust results replicated in a pool analysis merging different datasets from different analytic platforms. MDPI 2021-03-06 /pmc/articles/PMC7961481/ /pubmed/33800878 http://dx.doi.org/10.3390/ijms22052669 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
García-Mulero, Sandra
Alonso, Maria Henar
del Carpio, Luis P.
Sanz-Pamplona, Rebeca
Piulats, Josep M.
Additive Role of Immune System Infiltration and Angiogenesis in Uveal Melanoma Progression
title Additive Role of Immune System Infiltration and Angiogenesis in Uveal Melanoma Progression
title_full Additive Role of Immune System Infiltration and Angiogenesis in Uveal Melanoma Progression
title_fullStr Additive Role of Immune System Infiltration and Angiogenesis in Uveal Melanoma Progression
title_full_unstemmed Additive Role of Immune System Infiltration and Angiogenesis in Uveal Melanoma Progression
title_short Additive Role of Immune System Infiltration and Angiogenesis in Uveal Melanoma Progression
title_sort additive role of immune system infiltration and angiogenesis in uveal melanoma progression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961481/
https://www.ncbi.nlm.nih.gov/pubmed/33800878
http://dx.doi.org/10.3390/ijms22052669
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