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A Newly Established Cuproptosis-Related Gene Signature for Predicting Prognosis and Immune Infiltration in Uveal Melanoma

Uveal melanoma (UVM) is the most common primary ocular malignancy in adults and involves several types of regulated cell death. Cuproptosis is a novel method of regulating cell death by binding lipoylated TCA cycle proteins. There is still no research on the relationship between cuproptosis-related...

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Autores principales: Huang, Wei, Yang, Fan, Zhang, Yichi, Fang, Qianqi, Lai, Yitao, Lan, Yuqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10379443/
https://www.ncbi.nlm.nih.gov/pubmed/37511120
http://dx.doi.org/10.3390/ijms241411358
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author Huang, Wei
Yang, Fan
Zhang, Yichi
Fang, Qianqi
Lai, Yitao
Lan, Yuqing
author_facet Huang, Wei
Yang, Fan
Zhang, Yichi
Fang, Qianqi
Lai, Yitao
Lan, Yuqing
author_sort Huang, Wei
collection PubMed
description Uveal melanoma (UVM) is the most common primary ocular malignancy in adults and involves several types of regulated cell death. Cuproptosis is a novel method of regulating cell death by binding lipoylated TCA cycle proteins. There is still no research on the relationship between cuproptosis-related genes (CRGs) and UVM. Here, we aimed to develop a prognostic CRG signature for UVM. After a prognostic CRG signature was constructed, we determined the relationship between the signature and immune infiltration, bioinformatics analysis and experimental validation. Finally, a prognostic cuproptosis-related three-gene (CRTG) signature was constructed, which comprised ORAI2, ACADSB and SLC47A1. The risk score of the CRTG signature was negatively correlated with the overall survival (OS) and progression-free survival (PFS) of patients, which revealed strong predictive ability and its independent prognostic value. In addition, we found that the risk score was negative for chromosomes 3 and 6p, and positive for 8q, and high-risk UVM patients showed an increase in protumor immune infiltrates and a high expression of immune checkpoints. Finally, experimental validation verified that the migratory ability of MUM-2B cells was suppressed by the knockdown of the identified genes in vitro. We constructed a CRTG signature that is helpful in predicting prognosis and guiding treatment for patients with UVM.
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spelling pubmed-103794432023-07-29 A Newly Established Cuproptosis-Related Gene Signature for Predicting Prognosis and Immune Infiltration in Uveal Melanoma Huang, Wei Yang, Fan Zhang, Yichi Fang, Qianqi Lai, Yitao Lan, Yuqing Int J Mol Sci Article Uveal melanoma (UVM) is the most common primary ocular malignancy in adults and involves several types of regulated cell death. Cuproptosis is a novel method of regulating cell death by binding lipoylated TCA cycle proteins. There is still no research on the relationship between cuproptosis-related genes (CRGs) and UVM. Here, we aimed to develop a prognostic CRG signature for UVM. After a prognostic CRG signature was constructed, we determined the relationship between the signature and immune infiltration, bioinformatics analysis and experimental validation. Finally, a prognostic cuproptosis-related three-gene (CRTG) signature was constructed, which comprised ORAI2, ACADSB and SLC47A1. The risk score of the CRTG signature was negatively correlated with the overall survival (OS) and progression-free survival (PFS) of patients, which revealed strong predictive ability and its independent prognostic value. In addition, we found that the risk score was negative for chromosomes 3 and 6p, and positive for 8q, and high-risk UVM patients showed an increase in protumor immune infiltrates and a high expression of immune checkpoints. Finally, experimental validation verified that the migratory ability of MUM-2B cells was suppressed by the knockdown of the identified genes in vitro. We constructed a CRTG signature that is helpful in predicting prognosis and guiding treatment for patients with UVM. MDPI 2023-07-12 /pmc/articles/PMC10379443/ /pubmed/37511120 http://dx.doi.org/10.3390/ijms241411358 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Huang, Wei
Yang, Fan
Zhang, Yichi
Fang, Qianqi
Lai, Yitao
Lan, Yuqing
A Newly Established Cuproptosis-Related Gene Signature for Predicting Prognosis and Immune Infiltration in Uveal Melanoma
title A Newly Established Cuproptosis-Related Gene Signature for Predicting Prognosis and Immune Infiltration in Uveal Melanoma
title_full A Newly Established Cuproptosis-Related Gene Signature for Predicting Prognosis and Immune Infiltration in Uveal Melanoma
title_fullStr A Newly Established Cuproptosis-Related Gene Signature for Predicting Prognosis and Immune Infiltration in Uveal Melanoma
title_full_unstemmed A Newly Established Cuproptosis-Related Gene Signature for Predicting Prognosis and Immune Infiltration in Uveal Melanoma
title_short A Newly Established Cuproptosis-Related Gene Signature for Predicting Prognosis and Immune Infiltration in Uveal Melanoma
title_sort newly established cuproptosis-related gene signature for predicting prognosis and immune infiltration in uveal melanoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10379443/
https://www.ncbi.nlm.nih.gov/pubmed/37511120
http://dx.doi.org/10.3390/ijms241411358
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