IGFBPs were associated with stemness, inflammation, extracellular matrix remodeling and poor prognosis of low-grade glioma
BackgroundThe 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.MethodsWe validated the clinical value of the IGFBP family using RNA-seq and clini...
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.943300/full |
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| author | Zhihui Liu Zhihui Liu Zhihui Liu Hang Ji Wenchao Fu Wenchao Fu Shuai Ma Hongtao Zhao Hongtao Zhao Hongtao Zhao Fang Wang Fang Wang Jiawei Dong Jiawei Dong Xiuwei Yan Xiuwei Yan Jiheng Zhang Jiheng Zhang Nan Wang Nan Wang Jiasheng Wu Shaoshan Hu Shaoshan Hu |
| author_facet | Zhihui Liu Zhihui Liu Zhihui Liu Hang Ji Wenchao Fu Wenchao Fu Shuai Ma Hongtao Zhao Hongtao Zhao Hongtao Zhao Fang Wang Fang Wang Jiawei Dong Jiawei Dong Xiuwei Yan Xiuwei Yan Jiheng Zhang Jiheng Zhang Nan Wang Nan Wang Jiasheng Wu Shaoshan Hu Shaoshan Hu |
| author_sort | Zhihui Liu |
| collection | DOAJ |
| description | BackgroundThe 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.MethodsWe 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.ResultsOur 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.ConclusionOur 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. |
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| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-12T07:36:42Z |
| publishDate | 2022-08-01 |
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| series | Frontiers in Endocrinology |
| spelling | doaj.art-6d4c351c849940e89d00dd0c9506398c2022-12-22T03:41:55ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-08-011310.3389/fendo.2022.943300943300IGFBPs were associated with stemness, inflammation, extracellular matrix remodeling and poor prognosis of low-grade gliomaZhihui Liu0Zhihui Liu1Zhihui Liu2Hang Ji3Wenchao Fu4Wenchao Fu5Shuai Ma6Hongtao Zhao7Hongtao Zhao8Hongtao Zhao9Fang Wang10Fang Wang11Jiawei Dong12Jiawei Dong13Xiuwei Yan14Xiuwei Yan15Jiheng Zhang16Jiheng Zhang17Nan Wang18Nan Wang19Jiasheng Wu20Shaoshan Hu21Shaoshan Hu22Department of Neurosurgery, Cancer Center, Zhejiang Provincial People’s Hospital Affiliated to Hangzhou Medical College, Hangzhou, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaThe Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin, ChinaDepartment of Neurosurgery, West China Hospital, Sichuan University, Sichuan, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaThe Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, Cancer Center, Zhejiang Provincial People’s Hospital Affiliated to Hangzhou Medical College, Hangzhou, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaThe Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin, ChinaDepartment of Neurosurgery, Cancer Center, Zhejiang Provincial People’s Hospital Affiliated to Hangzhou Medical College, Hangzhou, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, Cancer Center, Zhejiang Provincial People’s Hospital Affiliated to Hangzhou Medical College, Hangzhou, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, Cancer Center, Zhejiang Provincial People’s Hospital Affiliated to Hangzhou Medical College, Hangzhou, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, Cancer Center, Zhejiang Provincial People’s Hospital Affiliated to Hangzhou Medical College, Hangzhou, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, Cancer Center, Zhejiang Provincial People’s Hospital Affiliated to Hangzhou Medical College, Hangzhou, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Neurosurgery, Cancer Center, Zhejiang Provincial People’s Hospital Affiliated to Hangzhou Medical College, Hangzhou, ChinaDepartment of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaBackgroundThe 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.MethodsWe 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.ResultsOur 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.ConclusionOur 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.https://www.frontiersin.org/articles/10.3389/fendo.2022.943300/fullextracellular matrixmetabolismstemnessinflammationinsulin-like growth factor binding protein (IGFBP) |
| spellingShingle | Zhihui Liu Zhihui Liu Zhihui Liu Hang Ji Wenchao Fu Wenchao Fu Shuai Ma Hongtao Zhao Hongtao Zhao Hongtao Zhao Fang Wang Fang Wang Jiawei Dong Jiawei Dong Xiuwei Yan Xiuwei Yan Jiheng Zhang Jiheng Zhang Nan Wang Nan Wang Jiasheng Wu Shaoshan Hu Shaoshan Hu IGFBPs were associated with stemness, inflammation, extracellular matrix remodeling and poor prognosis of low-grade glioma Frontiers in Endocrinology extracellular matrix metabolism stemness inflammation insulin-like growth factor binding protein (IGFBP) |
| 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 | extracellular matrix metabolism stemness inflammation insulin-like growth factor binding protein (IGFBP) |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.943300/full |
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