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IGFBPs were associated with stemness, inflammation, extracellular matrix remodeling and poor prognosis of low-grade glioma
BACKGROUND: The IGFBP family of insulin-like growth factor binding proteins has important biological functions in the organism. However, the role of the IGFBP family in low-grade glioma (LGG) has not been fully explored. METHODS: We validated the clinical value of the IGFBP family using RNA-seq and...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9381844/ https://www.ncbi.nlm.nih.gov/pubmed/35992105 http://dx.doi.org/10.3389/fendo.2022.943300 |
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author | Liu, Zhihui Ji, Hang Fu, Wenchao Ma, Shuai Zhao, Hongtao Wang, Fang Dong, Jiawei Yan, Xiuwei Zhang, Jiheng Wang, Nan Wu, Jiasheng Hu, Shaoshan |
author_facet | Liu, Zhihui Ji, Hang Fu, Wenchao Ma, Shuai Zhao, Hongtao Wang, Fang Dong, Jiawei Yan, Xiuwei Zhang, Jiheng Wang, Nan Wu, Jiasheng Hu, Shaoshan |
author_sort | Liu, Zhihui |
collection | PubMed |
description | BACKGROUND: The IGFBP family of insulin-like growth factor binding proteins has important biological functions in the organism. However, the role of the IGFBP family in low-grade glioma (LGG) has not been fully explored. METHODS: We validated the clinical value of the IGFBP family using RNA-seq and clinical data of LGG in the TCGA and constructed an IGFBPScore using LASSO-regression analysis for prognosis prediction, subtype determination, and treatment sensitivity determination. Subsequently, we explored the role of the IGFBP family in the development of LGG using PanCanAtlas data. RESULTS: Our results suggest that most IGFBP family members were aberrantly expressed and were strongly associated with poor prognosis in LGG. By constructing an IGFBPScore representing the IGFBP family, we found that tumor samples with a high IGFBPScore had a glioblastoma-like mutation pattern characterized by IDH1wt, EGFRmut, PTENmut, and NF1mut with hypo-methylation and glioma stem cell (GSC) diversity. In contrast, the low IGFBPScore group was characterized by IDH1mut accompanied by TP53mut, CICmut, and ATRXmut, and had hyper-methylation status as well as the GSC restriction. Additionally, the high-IGFBPScore group had a high inflammation phenotype with increased immune antigenicity and increased infiltration of immune molecules and cells, as well as a high extracellular matrix phenotype and enhanced multiple metabolic pathways compared with the immune-quiet phenotype of the low-IGFBPScore group, which was strongly associated with poor prognosis. CONCLUSION: Our study provides a summary analysis and a theoretical basis for the biological role and clinical value of the IGFBP family in LGG, providing an important therapeutic target for LGG. |
format | Online Article Text |
id | pubmed-9381844 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93818442022-08-18 IGFBPs were associated with stemness, inflammation, extracellular matrix remodeling and poor prognosis of low-grade glioma Liu, Zhihui Ji, Hang Fu, Wenchao Ma, Shuai Zhao, Hongtao Wang, Fang Dong, Jiawei Yan, Xiuwei Zhang, Jiheng Wang, Nan Wu, Jiasheng Hu, Shaoshan Front Endocrinol (Lausanne) Endocrinology BACKGROUND: The IGFBP family of insulin-like growth factor binding proteins has important biological functions in the organism. However, the role of the IGFBP family in low-grade glioma (LGG) has not been fully explored. METHODS: We validated the clinical value of the IGFBP family using RNA-seq and clinical data of LGG in the TCGA and constructed an IGFBPScore using LASSO-regression analysis for prognosis prediction, subtype determination, and treatment sensitivity determination. Subsequently, we explored the role of the IGFBP family in the development of LGG using PanCanAtlas data. RESULTS: Our results suggest that most IGFBP family members were aberrantly expressed and were strongly associated with poor prognosis in LGG. By constructing an IGFBPScore representing the IGFBP family, we found that tumor samples with a high IGFBPScore had a glioblastoma-like mutation pattern characterized by IDH1wt, EGFRmut, PTENmut, and NF1mut with hypo-methylation and glioma stem cell (GSC) diversity. In contrast, the low IGFBPScore group was characterized by IDH1mut accompanied by TP53mut, CICmut, and ATRXmut, and had hyper-methylation status as well as the GSC restriction. Additionally, the high-IGFBPScore group had a high inflammation phenotype with increased immune antigenicity and increased infiltration of immune molecules and cells, as well as a high extracellular matrix phenotype and enhanced multiple metabolic pathways compared with the immune-quiet phenotype of the low-IGFBPScore group, which was strongly associated with poor prognosis. CONCLUSION: Our study provides a summary analysis and a theoretical basis for the biological role and clinical value of the IGFBP family in LGG, providing an important therapeutic target for LGG. Frontiers Media S.A. 2022-08-03 /pmc/articles/PMC9381844/ /pubmed/35992105 http://dx.doi.org/10.3389/fendo.2022.943300 Text en Copyright © 2022 Liu, Ji, Fu, Ma, Zhao, Wang, Dong, Yan, Zhang, Wang, Wu and Hu 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 Liu, Zhihui Ji, Hang Fu, Wenchao Ma, Shuai Zhao, Hongtao Wang, Fang Dong, Jiawei Yan, Xiuwei Zhang, Jiheng Wang, Nan Wu, Jiasheng Hu, Shaoshan IGFBPs were associated with stemness, inflammation, extracellular matrix remodeling and poor prognosis of low-grade glioma |
title | IGFBPs were associated with stemness, inflammation, extracellular matrix remodeling and poor prognosis of low-grade glioma |
title_full | IGFBPs were associated with stemness, inflammation, extracellular matrix remodeling and poor prognosis of low-grade glioma |
title_fullStr | IGFBPs were associated with stemness, inflammation, extracellular matrix remodeling and poor prognosis of low-grade glioma |
title_full_unstemmed | IGFBPs were associated with stemness, inflammation, extracellular matrix remodeling and poor prognosis of low-grade glioma |
title_short | IGFBPs were associated with stemness, inflammation, extracellular matrix remodeling and poor prognosis of low-grade glioma |
title_sort | igfbps were associated with stemness, inflammation, extracellular matrix remodeling and poor prognosis of low-grade glioma |
topic | Endocrinology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9381844/ https://www.ncbi.nlm.nih.gov/pubmed/35992105 http://dx.doi.org/10.3389/fendo.2022.943300 |
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