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整合分析鉴定了人类脑胶质瘤的核心信号通路和缺氧特征。

Integrated analysis identified core signal pathways and hypoxic characteristics of human glioblastoma.

机构信息

Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Army Medical University (Third Military Medical University), and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, China.

Institute of Medicine and Equipment for High Altitude Region, College of High Altitude Military Medicine, Army Medical University, and Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Chongqing, China.

出版信息

J Cell Mol Med. 2019 Sep;23(9):6228-6237. doi: 10.1111/jcmm.14507. Epub 2019 Jul 7.

Abstract

As a hallmark for glioblastoma (GBM), high heterogeneity causes a variety of phenotypes and therapeutic responses among GBM patients, and it contributes to treatment failure. Moreover, hypoxia is a predominant feature of GBM and contributes greatly to its phenotype. To analyse the landscape of gene expression and hypoxic characteristics of GBM cells and their clinical significance in GBM patients, we performed transcriptome analysis of the GBM cell line U87-MG and the normal glial cell line HEB under normoxia and hypoxia conditions, with the results of which were analysed using established gene ontology databases as well as The Cancer Genome Atlas and the Cancer Cell Line Encyclopedia. We revealed core signal pathways, including inflammation, angiogenesis and migration, and for the first time mapped the components of the toll-like receptor 6 pathway in GBM cells. Moreover, by investigating the signal pathways involved in homoeostasis, proliferation and adenosine triphosphate metabolism, the critical response of GBM to hypoxia was clarified. Experiments with cell lines, patient serum and tissue identified IL1B, CSF3 and TIMP1 as potential plasma markers and VIM, STC1, TGFB1 and HMOX1 as potential biopsy markers for GBM. In conclusion, our study provided a comprehensive understanding for signal pathways and hypoxic characteristics of GBM and identified new biomarkers for GBM patients.

摘要

作为胶质母细胞瘤(GBM)的一个标志,高度异质性导致了 GBM 患者之间各种表型和治疗反应的出现,并导致了治疗失败。此外,缺氧是 GBM 的一个主要特征,对其表型有很大的贡献。为了分析 GBM 细胞的基因表达和缺氧特征及其在 GBM 患者中的临床意义,我们对 U87-MG 胶质母细胞瘤细胞系和正常神经胶质细胞系 HEB 在常氧和缺氧条件下进行了转录组分析,并使用已建立的基因本体数据库以及癌症基因组图谱和癌症细胞系百科全书对结果进行了分析。我们揭示了核心信号通路,包括炎症、血管生成和迁移,并且首次在 GBM 细胞中绘制了 Toll 样受体 6 途径的组成部分。此外,通过研究涉及体内平衡、增殖和三磷酸腺苷代谢的信号通路,阐明了 GBM 对缺氧的关键反应。通过细胞系、患者血清和组织的实验,鉴定出 IL1B、CSF3 和 TIMP1 作为潜在的血浆标志物,VIM、STC1、TGFB1 和 HMOX1 作为潜在的活检标志物用于 GBM。总之,我们的研究为 GBM 的信号通路和缺氧特征提供了全面的认识,并为 GBM 患者确定了新的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf8a/6714287/a5d3882fb7fa/JCMM-23-6228-g001.jpg

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