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Significance of NotchScore and JAG1 in predicting prognosis and immune response of low-grade glioma

INTRODUCTION: Low-grade glioma (LGG) is a prevalent malignant tumor in the intracranial region. Despite the advancements in treatment methods for this malignancy over the past decade, significant challenges still persist in the form of drug resistance and tumor recurrence. The Notch signaling pathwa...

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Autores principales: Shi, Bo, Ge, Fei, Cai, Liangliang, Yang, Yi, Guo, Xiaohui, Wu, Rui, Fan, Zhehao, Cao, Binjie, Wang, Ning, Si, Yue, Lin, Xinyue, Dong, Weibing, Sun, Haibo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10679421/
https://www.ncbi.nlm.nih.gov/pubmed/38022677
http://dx.doi.org/10.3389/fimmu.2023.1247288
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author Shi, Bo
Ge, Fei
Cai, Liangliang
Yang, Yi
Guo, Xiaohui
Wu, Rui
Fan, Zhehao
Cao, Binjie
Wang, Ning
Si, Yue
Lin, Xinyue
Dong, Weibing
Sun, Haibo
author_facet Shi, Bo
Ge, Fei
Cai, Liangliang
Yang, Yi
Guo, Xiaohui
Wu, Rui
Fan, Zhehao
Cao, Binjie
Wang, Ning
Si, Yue
Lin, Xinyue
Dong, Weibing
Sun, Haibo
author_sort Shi, Bo
collection PubMed
description INTRODUCTION: Low-grade glioma (LGG) is a prevalent malignant tumor in the intracranial region. Despite the advancements in treatment methods for this malignancy over the past decade, significant challenges still persist in the form of drug resistance and tumor recurrence. The Notch signaling pathway plays essential roles in many physiological processes as well as in cancer development. However, the significance of the pathway and family genes in LGG are poorly understood. METHODS: We conducted gene expression profiling analysis using the TCGA dataset to investigate the gene set associated with the Notch signaling pathway. we have proposed a metric called "NotchScore" that quantifies the strength of the Notch signaling pathway and enables us to assess its significance in predicting prognosis and immune response in LGG. We downregulated JAG1 in low-grade gliomas to assess its influence on the proliferation and migration of these tumors. Ultimately, we determined the impact of the transcription factor VDR on the transcription of PDL1 through chip-seq data analysis. RESULTS: Our findings indicate that tumors with a higher NotchScore, exhibit poorer prognosis, potentially due to their ability to evade the anti-tumor effects of immune cells by expressing immune checkpoints. Among the genes involved in the Notch signaling pathway, JAG1 has emerged as the most representative in terms of capturing the characteristics of both NotchScore and Notch pathways. The experimental results demonstrate that silencing JAG1 yielded a significant decrease in tumor cell proliferation in LGG cell lines. Our study revealed mechanisms by which tumors evade the immune system through the modulation of PDL1 transcription levels via the PI3K-Akt signaling pathway. Additionally, JAG1 potentially influences PDL1 in LGG by regulating the PI3K-Akt signaling pathway and the expression of the transcription factor VDR. DISCUSSION: These findings contribute to our understanding of immune evasion by tumors in LGG. The insights gained from this research may have implications for the development of therapeutic interventions for LGG.
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spelling pubmed-106794212023-01-01 Significance of NotchScore and JAG1 in predicting prognosis and immune response of low-grade glioma Shi, Bo Ge, Fei Cai, Liangliang Yang, Yi Guo, Xiaohui Wu, Rui Fan, Zhehao Cao, Binjie Wang, Ning Si, Yue Lin, Xinyue Dong, Weibing Sun, Haibo Front Immunol Immunology INTRODUCTION: Low-grade glioma (LGG) is a prevalent malignant tumor in the intracranial region. Despite the advancements in treatment methods for this malignancy over the past decade, significant challenges still persist in the form of drug resistance and tumor recurrence. The Notch signaling pathway plays essential roles in many physiological processes as well as in cancer development. However, the significance of the pathway and family genes in LGG are poorly understood. METHODS: We conducted gene expression profiling analysis using the TCGA dataset to investigate the gene set associated with the Notch signaling pathway. we have proposed a metric called "NotchScore" that quantifies the strength of the Notch signaling pathway and enables us to assess its significance in predicting prognosis and immune response in LGG. We downregulated JAG1 in low-grade gliomas to assess its influence on the proliferation and migration of these tumors. Ultimately, we determined the impact of the transcription factor VDR on the transcription of PDL1 through chip-seq data analysis. RESULTS: Our findings indicate that tumors with a higher NotchScore, exhibit poorer prognosis, potentially due to their ability to evade the anti-tumor effects of immune cells by expressing immune checkpoints. Among the genes involved in the Notch signaling pathway, JAG1 has emerged as the most representative in terms of capturing the characteristics of both NotchScore and Notch pathways. The experimental results demonstrate that silencing JAG1 yielded a significant decrease in tumor cell proliferation in LGG cell lines. Our study revealed mechanisms by which tumors evade the immune system through the modulation of PDL1 transcription levels via the PI3K-Akt signaling pathway. Additionally, JAG1 potentially influences PDL1 in LGG by regulating the PI3K-Akt signaling pathway and the expression of the transcription factor VDR. DISCUSSION: These findings contribute to our understanding of immune evasion by tumors in LGG. The insights gained from this research may have implications for the development of therapeutic interventions for LGG. Frontiers Media S.A. 2023-11-13 /pmc/articles/PMC10679421/ /pubmed/38022677 http://dx.doi.org/10.3389/fimmu.2023.1247288 Text en Copyright © 2023 Shi, Ge, Cai, Yang, Guo, Wu, Fan, Cao, Wang, Si, Lin, Dong and Sun 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 Immunology
Shi, Bo
Ge, Fei
Cai, Liangliang
Yang, Yi
Guo, Xiaohui
Wu, Rui
Fan, Zhehao
Cao, Binjie
Wang, Ning
Si, Yue
Lin, Xinyue
Dong, Weibing
Sun, Haibo
Significance of NotchScore and JAG1 in predicting prognosis and immune response of low-grade glioma
title Significance of NotchScore and JAG1 in predicting prognosis and immune response of low-grade glioma
title_full Significance of NotchScore and JAG1 in predicting prognosis and immune response of low-grade glioma
title_fullStr Significance of NotchScore and JAG1 in predicting prognosis and immune response of low-grade glioma
title_full_unstemmed Significance of NotchScore and JAG1 in predicting prognosis and immune response of low-grade glioma
title_short Significance of NotchScore and JAG1 in predicting prognosis and immune response of low-grade glioma
title_sort significance of notchscore and jag1 in predicting prognosis and immune response of low-grade glioma
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10679421/
https://www.ncbi.nlm.nih.gov/pubmed/38022677
http://dx.doi.org/10.3389/fimmu.2023.1247288
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