Cargando…
Development and validation of immunogenic cell death-related signature for predicting the prognosis and immune landscape of uveal melanoma
INTRODUCTION: Uveal melanoma (UM) is the most common primary intraocular malignant tumor in adults, and the main treatment for UM is currently surgery and plaque brachytherapy. UM is highly susceptible to metastasis, which eventually occurs in nearly half of all patients; once metastasis occurs, pat...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9709208/ https://www.ncbi.nlm.nih.gov/pubmed/36466923 http://dx.doi.org/10.3389/fimmu.2022.1037128 |
_version_ | 1784841097450618880 |
---|---|
author | Hu, Yuanyuan Cai, Jiayang Ye, Meng Mou, Qianxue Zhao, Bowen Sun, Qian Lou, Xiaotong Zhang, Hong Zhao, Yin |
author_facet | Hu, Yuanyuan Cai, Jiayang Ye, Meng Mou, Qianxue Zhao, Bowen Sun, Qian Lou, Xiaotong Zhang, Hong Zhao, Yin |
author_sort | Hu, Yuanyuan |
collection | PubMed |
description | INTRODUCTION: Uveal melanoma (UM) is the most common primary intraocular malignant tumor in adults, and the main treatment for UM is currently surgery and plaque brachytherapy. UM is highly susceptible to metastasis, which eventually occurs in nearly half of all patients; once metastasis occurs, patients have a poor prognosis and the condition is difficult to treat. Therefore, the identification of new and effective UM biomarkers is vital for the application of therapeutic strategies. Immunogenic cell death (ICD) is a type of regulatory cell death that activates adaptive immune responses and generates long-term immunological memory. ICD can promote antitumor immunity, which may be a potential immunotherapeutic strategy for UM. METHODS: The data of UM from the Cancer Genome Atlas (TCGA) was used as a training set and the data from Gene Expression Omnibus (GEO) was used as a validation set. To determine the expression pattern of ICD-related genes in UM, survival analysis and difference analysis was conducted. The ICD-related risk signature was constructed by employing the least absolute shrinkage and selection operator (LASSO) Cox regression. Subsequently, immune profile and somatic mutation analysis were performed. In addition, cell experiments were performed to verify the role of immunogenic cell death-related genes in UM. RESULTS: In this study, we analyzed the relationship between ICD-related gene expression and UM patient prognosis, somatic mutations, and the tumor immune microenvironment. Importantly, we constructed a 5-gene ICD-related risk signature and confirmed it as a novel prognostic biomarker in UM patients. We found that the high-risk group had more immune cell infiltration and a worse prognosis than the low-risk group. In cellular experiments, we confirmed the high expression of FOXP3 inMUM2B andOCM-1A cell lines and that knockdown of FOXP3 markedly inhibited the proliferation of UM tumor cells. DISCUSSION: ICD-related genes play a critical role in the tumor immune microenvironment. Our results may contribute to the development of effective immunotherapies. |
format | Online Article Text |
id | pubmed-9709208 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-97092082022-12-01 Development and validation of immunogenic cell death-related signature for predicting the prognosis and immune landscape of uveal melanoma Hu, Yuanyuan Cai, Jiayang Ye, Meng Mou, Qianxue Zhao, Bowen Sun, Qian Lou, Xiaotong Zhang, Hong Zhao, Yin Front Immunol Immunology INTRODUCTION: Uveal melanoma (UM) is the most common primary intraocular malignant tumor in adults, and the main treatment for UM is currently surgery and plaque brachytherapy. UM is highly susceptible to metastasis, which eventually occurs in nearly half of all patients; once metastasis occurs, patients have a poor prognosis and the condition is difficult to treat. Therefore, the identification of new and effective UM biomarkers is vital for the application of therapeutic strategies. Immunogenic cell death (ICD) is a type of regulatory cell death that activates adaptive immune responses and generates long-term immunological memory. ICD can promote antitumor immunity, which may be a potential immunotherapeutic strategy for UM. METHODS: The data of UM from the Cancer Genome Atlas (TCGA) was used as a training set and the data from Gene Expression Omnibus (GEO) was used as a validation set. To determine the expression pattern of ICD-related genes in UM, survival analysis and difference analysis was conducted. The ICD-related risk signature was constructed by employing the least absolute shrinkage and selection operator (LASSO) Cox regression. Subsequently, immune profile and somatic mutation analysis were performed. In addition, cell experiments were performed to verify the role of immunogenic cell death-related genes in UM. RESULTS: In this study, we analyzed the relationship between ICD-related gene expression and UM patient prognosis, somatic mutations, and the tumor immune microenvironment. Importantly, we constructed a 5-gene ICD-related risk signature and confirmed it as a novel prognostic biomarker in UM patients. We found that the high-risk group had more immune cell infiltration and a worse prognosis than the low-risk group. In cellular experiments, we confirmed the high expression of FOXP3 inMUM2B andOCM-1A cell lines and that knockdown of FOXP3 markedly inhibited the proliferation of UM tumor cells. DISCUSSION: ICD-related genes play a critical role in the tumor immune microenvironment. Our results may contribute to the development of effective immunotherapies. Frontiers Media S.A. 2022-11-16 /pmc/articles/PMC9709208/ /pubmed/36466923 http://dx.doi.org/10.3389/fimmu.2022.1037128 Text en Copyright © 2022 Hu, Cai, Ye, Mou, Zhao, Sun, Lou, Zhang and Zhao 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 | Immunology Hu, Yuanyuan Cai, Jiayang Ye, Meng Mou, Qianxue Zhao, Bowen Sun, Qian Lou, Xiaotong Zhang, Hong Zhao, Yin Development and validation of immunogenic cell death-related signature for predicting the prognosis and immune landscape of uveal melanoma |
title | Development and validation of immunogenic cell death-related signature for predicting the prognosis and immune landscape of uveal melanoma |
title_full | Development and validation of immunogenic cell death-related signature for predicting the prognosis and immune landscape of uveal melanoma |
title_fullStr | Development and validation of immunogenic cell death-related signature for predicting the prognosis and immune landscape of uveal melanoma |
title_full_unstemmed | Development and validation of immunogenic cell death-related signature for predicting the prognosis and immune landscape of uveal melanoma |
title_short | Development and validation of immunogenic cell death-related signature for predicting the prognosis and immune landscape of uveal melanoma |
title_sort | development and validation of immunogenic cell death-related signature for predicting the prognosis and immune landscape of uveal melanoma |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9709208/ https://www.ncbi.nlm.nih.gov/pubmed/36466923 http://dx.doi.org/10.3389/fimmu.2022.1037128 |
work_keys_str_mv | AT huyuanyuan developmentandvalidationofimmunogeniccelldeathrelatedsignatureforpredictingtheprognosisandimmunelandscapeofuvealmelanoma AT caijiayang developmentandvalidationofimmunogeniccelldeathrelatedsignatureforpredictingtheprognosisandimmunelandscapeofuvealmelanoma AT yemeng developmentandvalidationofimmunogeniccelldeathrelatedsignatureforpredictingtheprognosisandimmunelandscapeofuvealmelanoma AT mouqianxue developmentandvalidationofimmunogeniccelldeathrelatedsignatureforpredictingtheprognosisandimmunelandscapeofuvealmelanoma AT zhaobowen developmentandvalidationofimmunogeniccelldeathrelatedsignatureforpredictingtheprognosisandimmunelandscapeofuvealmelanoma AT sunqian developmentandvalidationofimmunogeniccelldeathrelatedsignatureforpredictingtheprognosisandimmunelandscapeofuvealmelanoma AT louxiaotong developmentandvalidationofimmunogeniccelldeathrelatedsignatureforpredictingtheprognosisandimmunelandscapeofuvealmelanoma AT zhanghong developmentandvalidationofimmunogeniccelldeathrelatedsignatureforpredictingtheprognosisandimmunelandscapeofuvealmelanoma AT zhaoyin developmentandvalidationofimmunogeniccelldeathrelatedsignatureforpredictingtheprognosisandimmunelandscapeofuvealmelanoma |