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Identification of Precise Therapeutic Targets and Characteristic Prognostic Genes Based on Immune Gene Characteristics in Uveal Melanoma

The tumor microenvironment is an important factor for the immunotherapy of tumor patients. The sequenced transcriptome data can be used to describe the tumor microenvironment and various immune subtypes. We exploited published data on patients with uveal melanoma (UVM) to identify immune subtypes. B...

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Autores principales: Zhang, Zhenxi, Su, Jingyu, Li, Li, Du, Wenjing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187912/
https://www.ncbi.nlm.nih.gov/pubmed/34124047
http://dx.doi.org/10.3389/fcell.2021.666462
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author Zhang, Zhenxi
Su, Jingyu
Li, Li
Du, Wenjing
author_facet Zhang, Zhenxi
Su, Jingyu
Li, Li
Du, Wenjing
author_sort Zhang, Zhenxi
collection PubMed
description The tumor microenvironment is an important factor for the immunotherapy of tumor patients. The sequenced transcriptome data can be used to describe the tumor microenvironment and various immune subtypes. We exploited published data on patients with uveal melanoma (UVM) to identify immune subtypes. Based on the immune-related gene sets of 80 patients with UVM in the TCGA database, we used consensus clustering to identify two immune subgroups. In the two immune subtypes, we analyzed clinical characteristics and immune infiltration. Class1 has low immune infiltration, contains memory B cells, Th2 cells, Th17 cells, eosinophils, natural killer cells, and has a better prognosis. Class2 has higher immune infiltration. CD8+ T cells, Th1 cells, MDSCs, and Dendritic cells are enriched in class2, which has strong cytolytic activity, high expression of immune checkpoint genes, and poor outcome. Moreover, we have developed and verified an immune characteristic model that can predict the prognosis of patients well. Through this model, we screened prostaglandin-endoperoxide synthase 2 (PTGS2) as the therapeutic target of UVM. Treatment of choroidal melanoma cell line (OCM1) cells with celecoxib (an inhibitor of PTGS2) effectively inhibits cell growth, proliferation, and promotes apoptosis. Our results show the immunological heterogeneity of UVM patients and also provide an ideal therapeutic target for the future treatment design of patients.
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spelling pubmed-81879122021-06-10 Identification of Precise Therapeutic Targets and Characteristic Prognostic Genes Based on Immune Gene Characteristics in Uveal Melanoma Zhang, Zhenxi Su, Jingyu Li, Li Du, Wenjing Front Cell Dev Biol Cell and Developmental Biology The tumor microenvironment is an important factor for the immunotherapy of tumor patients. The sequenced transcriptome data can be used to describe the tumor microenvironment and various immune subtypes. We exploited published data on patients with uveal melanoma (UVM) to identify immune subtypes. Based on the immune-related gene sets of 80 patients with UVM in the TCGA database, we used consensus clustering to identify two immune subgroups. In the two immune subtypes, we analyzed clinical characteristics and immune infiltration. Class1 has low immune infiltration, contains memory B cells, Th2 cells, Th17 cells, eosinophils, natural killer cells, and has a better prognosis. Class2 has higher immune infiltration. CD8+ T cells, Th1 cells, MDSCs, and Dendritic cells are enriched in class2, which has strong cytolytic activity, high expression of immune checkpoint genes, and poor outcome. Moreover, we have developed and verified an immune characteristic model that can predict the prognosis of patients well. Through this model, we screened prostaglandin-endoperoxide synthase 2 (PTGS2) as the therapeutic target of UVM. Treatment of choroidal melanoma cell line (OCM1) cells with celecoxib (an inhibitor of PTGS2) effectively inhibits cell growth, proliferation, and promotes apoptosis. Our results show the immunological heterogeneity of UVM patients and also provide an ideal therapeutic target for the future treatment design of patients. Frontiers Media S.A. 2021-05-26 /pmc/articles/PMC8187912/ /pubmed/34124047 http://dx.doi.org/10.3389/fcell.2021.666462 Text en Copyright © 2021 Zhang, Su, Li and Du. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Zhang, Zhenxi
Su, Jingyu
Li, Li
Du, Wenjing
Identification of Precise Therapeutic Targets and Characteristic Prognostic Genes Based on Immune Gene Characteristics in Uveal Melanoma
title Identification of Precise Therapeutic Targets and Characteristic Prognostic Genes Based on Immune Gene Characteristics in Uveal Melanoma
title_full Identification of Precise Therapeutic Targets and Characteristic Prognostic Genes Based on Immune Gene Characteristics in Uveal Melanoma
title_fullStr Identification of Precise Therapeutic Targets and Characteristic Prognostic Genes Based on Immune Gene Characteristics in Uveal Melanoma
title_full_unstemmed Identification of Precise Therapeutic Targets and Characteristic Prognostic Genes Based on Immune Gene Characteristics in Uveal Melanoma
title_short Identification of Precise Therapeutic Targets and Characteristic Prognostic Genes Based on Immune Gene Characteristics in Uveal Melanoma
title_sort identification of precise therapeutic targets and characteristic prognostic genes based on immune gene characteristics in uveal melanoma
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187912/
https://www.ncbi.nlm.nih.gov/pubmed/34124047
http://dx.doi.org/10.3389/fcell.2021.666462
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