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Comprehensive analysis of the clinical and biological significances of cholesterol metabolism in lower-grade gliomas

BACKGROUND: As a component of membrane lipids and the precursor of oxysterols and steroid hormones, reprogrammed cholesterol metabolism contributes to the initiation and progression of multiple cancers. Thus, we aim to further investigate the significances of cholesterol metabolism in lower-grade gl...

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Autores principales: Tao, Rui, Huang, Ruoyu, Yang, Jingchen, Wang, Jiangfei, Wang, Kuanyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10364387/
https://www.ncbi.nlm.nih.gov/pubmed/37488496
http://dx.doi.org/10.1186/s12885-023-10897-0
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author Tao, Rui
Huang, Ruoyu
Yang, Jingchen
Wang, Jiangfei
Wang, Kuanyu
author_facet Tao, Rui
Huang, Ruoyu
Yang, Jingchen
Wang, Jiangfei
Wang, Kuanyu
author_sort Tao, Rui
collection PubMed
description BACKGROUND: As a component of membrane lipids and the precursor of oxysterols and steroid hormones, reprogrammed cholesterol metabolism contributes to the initiation and progression of multiple cancers. Thus, we aim to further investigate the significances of cholesterol metabolism in lower-grade gliomas (LGGs). METHODS: The present study included 413 LGG samples from TCGA RNA-seq dataset (training cohort) and 172 LGG samples from CGGA RNA-seq dataset (validation cohort). The cholesterol metabolism-related signature was identified by the LASSO regression model. Bioinformatics analyses were performed to explore the functional roles of this signature in LGGs. Kaplan-Meier and Cox regression analyses were enrolled to estimate prognostic value of the risk signature. RESULTS: Our findings suggested that cholesterol metabolism was tightly associated clinicopathologic features and genomic alterations of LGGs. Bioinformatics analyses revealed that cholesterol metabolism played a key role in immunosuppression of LGGs, mainly by promoting macrophages polarization and T cell exhaustion. Kaplan-Meier curve and Cox regression analysis showed that cholesterol metabolism was an independent prognostic indicator for LGG patients. To improve the clinical application value of the risk signature, we also constructed a nomogram model to predict the 1-, 3- and 5-year survival of LGG patients. CONCLUSION: The cholesterol metabolism was powerful prognostic indicator and could serve as a promising target to enhance personalized treatment of LGGs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-10897-0.
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spelling pubmed-103643872023-07-25 Comprehensive analysis of the clinical and biological significances of cholesterol metabolism in lower-grade gliomas Tao, Rui Huang, Ruoyu Yang, Jingchen Wang, Jiangfei Wang, Kuanyu BMC Cancer Research BACKGROUND: As a component of membrane lipids and the precursor of oxysterols and steroid hormones, reprogrammed cholesterol metabolism contributes to the initiation and progression of multiple cancers. Thus, we aim to further investigate the significances of cholesterol metabolism in lower-grade gliomas (LGGs). METHODS: The present study included 413 LGG samples from TCGA RNA-seq dataset (training cohort) and 172 LGG samples from CGGA RNA-seq dataset (validation cohort). The cholesterol metabolism-related signature was identified by the LASSO regression model. Bioinformatics analyses were performed to explore the functional roles of this signature in LGGs. Kaplan-Meier and Cox regression analyses were enrolled to estimate prognostic value of the risk signature. RESULTS: Our findings suggested that cholesterol metabolism was tightly associated clinicopathologic features and genomic alterations of LGGs. Bioinformatics analyses revealed that cholesterol metabolism played a key role in immunosuppression of LGGs, mainly by promoting macrophages polarization and T cell exhaustion. Kaplan-Meier curve and Cox regression analysis showed that cholesterol metabolism was an independent prognostic indicator for LGG patients. To improve the clinical application value of the risk signature, we also constructed a nomogram model to predict the 1-, 3- and 5-year survival of LGG patients. CONCLUSION: The cholesterol metabolism was powerful prognostic indicator and could serve as a promising target to enhance personalized treatment of LGGs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-10897-0. BioMed Central 2023-07-24 /pmc/articles/PMC10364387/ /pubmed/37488496 http://dx.doi.org/10.1186/s12885-023-10897-0 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Tao, Rui
Huang, Ruoyu
Yang, Jingchen
Wang, Jiangfei
Wang, Kuanyu
Comprehensive analysis of the clinical and biological significances of cholesterol metabolism in lower-grade gliomas
title Comprehensive analysis of the clinical and biological significances of cholesterol metabolism in lower-grade gliomas
title_full Comprehensive analysis of the clinical and biological significances of cholesterol metabolism in lower-grade gliomas
title_fullStr Comprehensive analysis of the clinical and biological significances of cholesterol metabolism in lower-grade gliomas
title_full_unstemmed Comprehensive analysis of the clinical and biological significances of cholesterol metabolism in lower-grade gliomas
title_short Comprehensive analysis of the clinical and biological significances of cholesterol metabolism in lower-grade gliomas
title_sort comprehensive analysis of the clinical and biological significances of cholesterol metabolism in lower-grade gliomas
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10364387/
https://www.ncbi.nlm.nih.gov/pubmed/37488496
http://dx.doi.org/10.1186/s12885-023-10897-0
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