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Integrating multiple machine learning methods to construct glutamine metabolism-related signatures in lung adenocarcinoma
BACKGROUND: Glutamine metabolism (GM) is known to play a critical role in cancer development, including in lung adenocarcinoma (LUAD), although the exact contribution of GM to LUAD remains incompletely understood. In this study, we aimed to discover new targets for the treatment of LUAD patients by...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10229769/ https://www.ncbi.nlm.nih.gov/pubmed/37265698 http://dx.doi.org/10.3389/fendo.2023.1196372 |
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author | Zhang, Pengpeng Pei, Shengbin Wu, Leilei Xia, Zhijia Wang, Qi Huang, Xufeng Li, Zhangzuo Xie, Jiaheng Du, Mingjun Lin, Haoran |
author_facet | Zhang, Pengpeng Pei, Shengbin Wu, Leilei Xia, Zhijia Wang, Qi Huang, Xufeng Li, Zhangzuo Xie, Jiaheng Du, Mingjun Lin, Haoran |
author_sort | Zhang, Pengpeng |
collection | PubMed |
description | BACKGROUND: Glutamine metabolism (GM) is known to play a critical role in cancer development, including in lung adenocarcinoma (LUAD), although the exact contribution of GM to LUAD remains incompletely understood. In this study, we aimed to discover new targets for the treatment of LUAD patients by using machine learning algorithms to establish prognostic models based on GM-related genes (GMRGs). METHODS: We used the AUCell and WGCNA algorithms, along with single-cell and bulk RNA-seq data, to identify the most prominent GMRGs associated with LUAD. Multiple machine learning algorithms were employed to develop risk models with optimal predictive performance. We validated our models using multiple external datasets and investigated disparities in the tumor microenvironment (TME), mutation landscape, enriched pathways, and response to immunotherapy across various risk groups. Additionally, we conducted in vitro and in vivo experiments to confirm the role of LGALS3 in LUAD. RESULTS: We identified 173 GMRGs strongly associated with GM activity and selected the Random Survival Forest (RSF) and Supervised Principal Components (SuperPC) methods to develop a prognostic model. Our model’s performance was validated using multiple external datasets. Our analysis revealed that the low-risk group had higher immune cell infiltration and increased expression of immune checkpoints, indicating that this group may be more receptive to immunotherapy. Moreover, our experimental results confirmed that LGALS3 promoted the proliferation, invasion, and migration of LUAD cells. CONCLUSION: Our study established a prognostic model based on GMRGs that can predict the effectiveness of immunotherapy and provide novel approaches for the treatment of LUAD. Our findings also suggest that LGALS3 may be a potential therapeutic target for LUAD. |
format | Online Article Text |
id | pubmed-10229769 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-102297692023-06-01 Integrating multiple machine learning methods to construct glutamine metabolism-related signatures in lung adenocarcinoma Zhang, Pengpeng Pei, Shengbin Wu, Leilei Xia, Zhijia Wang, Qi Huang, Xufeng Li, Zhangzuo Xie, Jiaheng Du, Mingjun Lin, Haoran Front Endocrinol (Lausanne) Endocrinology BACKGROUND: Glutamine metabolism (GM) is known to play a critical role in cancer development, including in lung adenocarcinoma (LUAD), although the exact contribution of GM to LUAD remains incompletely understood. In this study, we aimed to discover new targets for the treatment of LUAD patients by using machine learning algorithms to establish prognostic models based on GM-related genes (GMRGs). METHODS: We used the AUCell and WGCNA algorithms, along with single-cell and bulk RNA-seq data, to identify the most prominent GMRGs associated with LUAD. Multiple machine learning algorithms were employed to develop risk models with optimal predictive performance. We validated our models using multiple external datasets and investigated disparities in the tumor microenvironment (TME), mutation landscape, enriched pathways, and response to immunotherapy across various risk groups. Additionally, we conducted in vitro and in vivo experiments to confirm the role of LGALS3 in LUAD. RESULTS: We identified 173 GMRGs strongly associated with GM activity and selected the Random Survival Forest (RSF) and Supervised Principal Components (SuperPC) methods to develop a prognostic model. Our model’s performance was validated using multiple external datasets. Our analysis revealed that the low-risk group had higher immune cell infiltration and increased expression of immune checkpoints, indicating that this group may be more receptive to immunotherapy. Moreover, our experimental results confirmed that LGALS3 promoted the proliferation, invasion, and migration of LUAD cells. CONCLUSION: Our study established a prognostic model based on GMRGs that can predict the effectiveness of immunotherapy and provide novel approaches for the treatment of LUAD. Our findings also suggest that LGALS3 may be a potential therapeutic target for LUAD. Frontiers Media S.A. 2023-05-17 /pmc/articles/PMC10229769/ /pubmed/37265698 http://dx.doi.org/10.3389/fendo.2023.1196372 Text en Copyright © 2023 Zhang, Pei, Wu, Xia, Wang, Huang, Li, Xie, Du and Lin 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 | Endocrinology Zhang, Pengpeng Pei, Shengbin Wu, Leilei Xia, Zhijia Wang, Qi Huang, Xufeng Li, Zhangzuo Xie, Jiaheng Du, Mingjun Lin, Haoran Integrating multiple machine learning methods to construct glutamine metabolism-related signatures in lung adenocarcinoma |
title | Integrating multiple machine learning methods to construct glutamine metabolism-related signatures in lung adenocarcinoma |
title_full | Integrating multiple machine learning methods to construct glutamine metabolism-related signatures in lung adenocarcinoma |
title_fullStr | Integrating multiple machine learning methods to construct glutamine metabolism-related signatures in lung adenocarcinoma |
title_full_unstemmed | Integrating multiple machine learning methods to construct glutamine metabolism-related signatures in lung adenocarcinoma |
title_short | Integrating multiple machine learning methods to construct glutamine metabolism-related signatures in lung adenocarcinoma |
title_sort | integrating multiple machine learning methods to construct glutamine metabolism-related signatures in lung adenocarcinoma |
topic | Endocrinology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10229769/ https://www.ncbi.nlm.nih.gov/pubmed/37265698 http://dx.doi.org/10.3389/fendo.2023.1196372 |
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