Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Zhihui, Ji, Hang, Fu, Wenchao, Ma, Shuai, Zhao, Hongtao, Wang, Fang, Dong, Jiawei, Yan, Xiuwei, Zhang, Jiheng, Wang, Nan, Wu, Jiasheng, Hu, Shaoshan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
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
_version_ 1784769164571836416
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
work_keys_str_mv AT liuzhihui igfbpswereassociatedwithstemnessinflammationextracellularmatrixremodelingandpoorprognosisoflowgradeglioma
AT jihang igfbpswereassociatedwithstemnessinflammationextracellularmatrixremodelingandpoorprognosisoflowgradeglioma
AT fuwenchao igfbpswereassociatedwithstemnessinflammationextracellularmatrixremodelingandpoorprognosisoflowgradeglioma
AT mashuai igfbpswereassociatedwithstemnessinflammationextracellularmatrixremodelingandpoorprognosisoflowgradeglioma
AT zhaohongtao igfbpswereassociatedwithstemnessinflammationextracellularmatrixremodelingandpoorprognosisoflowgradeglioma
AT wangfang igfbpswereassociatedwithstemnessinflammationextracellularmatrixremodelingandpoorprognosisoflowgradeglioma
AT dongjiawei igfbpswereassociatedwithstemnessinflammationextracellularmatrixremodelingandpoorprognosisoflowgradeglioma
AT yanxiuwei igfbpswereassociatedwithstemnessinflammationextracellularmatrixremodelingandpoorprognosisoflowgradeglioma
AT zhangjiheng igfbpswereassociatedwithstemnessinflammationextracellularmatrixremodelingandpoorprognosisoflowgradeglioma
AT wangnan igfbpswereassociatedwithstemnessinflammationextracellularmatrixremodelingandpoorprognosisoflowgradeglioma
AT wujiasheng igfbpswereassociatedwithstemnessinflammationextracellularmatrixremodelingandpoorprognosisoflowgradeglioma
AT hushaoshan igfbpswereassociatedwithstemnessinflammationextracellularmatrixremodelingandpoorprognosisoflowgradeglioma