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Identification of cuproptosis-related subtypes and the development of a prognostic model in glioma

Introduction: A copper-dependent cell death, cuproptosis, involves copper binding with lipoylated tricarboxylic acid (TCA) cycle components. In cuproptosis, ferredoxin 1 (FDX1) and lipoylation act as key regulators. The mechanism of cuproptosis differs from the current knowledge of cell death, which...

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Autores principales: Wu, Zhaoping, Li, Wei, Zhu, Hecheng, Li, Xuewen, Zhou, Yi, Chen, Quan, Huang, Haoxuan, Zhang, Wenlong, Jiang, Xingjun, Ren, Caiping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10014798/
https://www.ncbi.nlm.nih.gov/pubmed/36936439
http://dx.doi.org/10.3389/fgene.2023.1124439
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author Wu, Zhaoping
Li, Wei
Zhu, Hecheng
Li, Xuewen
Zhou, Yi
Chen, Quan
Huang, Haoxuan
Zhang, Wenlong
Jiang, Xingjun
Ren, Caiping
author_facet Wu, Zhaoping
Li, Wei
Zhu, Hecheng
Li, Xuewen
Zhou, Yi
Chen, Quan
Huang, Haoxuan
Zhang, Wenlong
Jiang, Xingjun
Ren, Caiping
author_sort Wu, Zhaoping
collection PubMed
description Introduction: A copper-dependent cell death, cuproptosis, involves copper binding with lipoylated tricarboxylic acid (TCA) cycle components. In cuproptosis, ferredoxin 1 (FDX1) and lipoylation act as key regulators. The mechanism of cuproptosis differs from the current knowledge of cell death, which may invigorate investigations into copper’s potential as a cancer treatment. An extremely dismal prognosis is associated with gliomas, the most prevalent primary intracranial tumor. In patients with glioma, conventional therapies, such as surgery and chemotherapy, have shown limited improvement. A variety of cell death modes have been confirmed to be operative in glioma oncogenesis and participate in the tumor microenvironment (TME), implicated in glioma development and progression. In this study, we aimed to explore whether cuproptosis influences glioma oncogenesis. Methods: Gene expression profiles related to cuproptosis were comprehensively evaluated by comparing adjacent tissues from glioma tissues in The Cancer Genome Atlas (TCGA) (https://portal.gdc.cancer.gov/) database. Gene expression, prognostic, clinical, and pathological data of lower-grade gliomas (LGG) and glioblastoma were retrieved from TCGA and Gene Expression Omnibus (GEO) (https://www.ncbi.nlm.nih.gov/geo/) databases. The datasets were managed by “Combat” algorithm to eliminate batch effects and then combined. A consensus clustering algorithm based on the Partitioning Around Medoid (PAM) algorithm was used to classified 725 patients with LGG and glioblastoma multiforme (GBM) into two cuproptosis subtypes. According to the differentially expressed genes in the two cuproptosis subtypes, 725 patients were divided into 2 gene subtypes. Additionally, a scoring system that associated with TME was constructed to predict patient survival and patient immunotherapy outcomes. Furthermore, we constructed a prognostic CRG-score and nomogram system to predict the prognosis of glioma patients. 95 tissue specimens from 83 glioma patients undergoing surgical treatment were collected, including adjacent tissues. Using immunohistochemistry and RT-qPCR, we verified cuproptosis-related genes expression and CRG-score predictive ability in these clinical samples. Results: Our results revealed extensive regulatory mechanisms of cuproptosis-related genes in the cell cycle, TME, clinicopathological characteristics, and prognosis of glioma. We also developed a prognostic model based on cuproptosis. Through the verifications of database and clinical samples, we believe that cuproptosis affects the prognosis of glioma and potentially provides novel glioma research approaches. Conclusion: We suggest that cuproptosis has potential importance in treating gliomas and could be utilized in new glioma research efforts.
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spelling pubmed-100147982023-03-16 Identification of cuproptosis-related subtypes and the development of a prognostic model in glioma Wu, Zhaoping Li, Wei Zhu, Hecheng Li, Xuewen Zhou, Yi Chen, Quan Huang, Haoxuan Zhang, Wenlong Jiang, Xingjun Ren, Caiping Front Genet Genetics Introduction: A copper-dependent cell death, cuproptosis, involves copper binding with lipoylated tricarboxylic acid (TCA) cycle components. In cuproptosis, ferredoxin 1 (FDX1) and lipoylation act as key regulators. The mechanism of cuproptosis differs from the current knowledge of cell death, which may invigorate investigations into copper’s potential as a cancer treatment. An extremely dismal prognosis is associated with gliomas, the most prevalent primary intracranial tumor. In patients with glioma, conventional therapies, such as surgery and chemotherapy, have shown limited improvement. A variety of cell death modes have been confirmed to be operative in glioma oncogenesis and participate in the tumor microenvironment (TME), implicated in glioma development and progression. In this study, we aimed to explore whether cuproptosis influences glioma oncogenesis. Methods: Gene expression profiles related to cuproptosis were comprehensively evaluated by comparing adjacent tissues from glioma tissues in The Cancer Genome Atlas (TCGA) (https://portal.gdc.cancer.gov/) database. Gene expression, prognostic, clinical, and pathological data of lower-grade gliomas (LGG) and glioblastoma were retrieved from TCGA and Gene Expression Omnibus (GEO) (https://www.ncbi.nlm.nih.gov/geo/) databases. The datasets were managed by “Combat” algorithm to eliminate batch effects and then combined. A consensus clustering algorithm based on the Partitioning Around Medoid (PAM) algorithm was used to classified 725 patients with LGG and glioblastoma multiforme (GBM) into two cuproptosis subtypes. According to the differentially expressed genes in the two cuproptosis subtypes, 725 patients were divided into 2 gene subtypes. Additionally, a scoring system that associated with TME was constructed to predict patient survival and patient immunotherapy outcomes. Furthermore, we constructed a prognostic CRG-score and nomogram system to predict the prognosis of glioma patients. 95 tissue specimens from 83 glioma patients undergoing surgical treatment were collected, including adjacent tissues. Using immunohistochemistry and RT-qPCR, we verified cuproptosis-related genes expression and CRG-score predictive ability in these clinical samples. Results: Our results revealed extensive regulatory mechanisms of cuproptosis-related genes in the cell cycle, TME, clinicopathological characteristics, and prognosis of glioma. We also developed a prognostic model based on cuproptosis. Through the verifications of database and clinical samples, we believe that cuproptosis affects the prognosis of glioma and potentially provides novel glioma research approaches. Conclusion: We suggest that cuproptosis has potential importance in treating gliomas and could be utilized in new glioma research efforts. Frontiers Media S.A. 2023-03-01 /pmc/articles/PMC10014798/ /pubmed/36936439 http://dx.doi.org/10.3389/fgene.2023.1124439 Text en Copyright © 2023 Wu, Li, Zhu, Li, Zhou, Chen, Huang, Zhang, Jiang and Ren. 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 Genetics
Wu, Zhaoping
Li, Wei
Zhu, Hecheng
Li, Xuewen
Zhou, Yi
Chen, Quan
Huang, Haoxuan
Zhang, Wenlong
Jiang, Xingjun
Ren, Caiping
Identification of cuproptosis-related subtypes and the development of a prognostic model in glioma
title Identification of cuproptosis-related subtypes and the development of a prognostic model in glioma
title_full Identification of cuproptosis-related subtypes and the development of a prognostic model in glioma
title_fullStr Identification of cuproptosis-related subtypes and the development of a prognostic model in glioma
title_full_unstemmed Identification of cuproptosis-related subtypes and the development of a prognostic model in glioma
title_short Identification of cuproptosis-related subtypes and the development of a prognostic model in glioma
title_sort identification of cuproptosis-related subtypes and the development of a prognostic model in glioma
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10014798/
https://www.ncbi.nlm.nih.gov/pubmed/36936439
http://dx.doi.org/10.3389/fgene.2023.1124439
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