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Receptor tyrosine kinase expression in high-grade gliomas before and after chemoradiotherapy

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机构: [a]Department of Gamma Knife Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China [b]Department of Neurosurgery, Beijing Neurosurgical Institute, China [c]Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, China [d]Department of Neuropathology, Beijing Neurosurgical Institute, China [e]Department of Radiotherapy, Beijing Tiantan Hospital, Capital Medical University, 6 Tiantan Xili, Dongcheng, Beijing, 100050, China
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关键词: Biomarker Chemoradiotherapy Glioblastoma Glioma Receptor tyrosine kinases

摘要:
Glioma is the most common type of malignant brain tumor, and is characterized by invasive growth and chemoradiotherapy resistance. The following Cancer Genome Atlas mutation subtypes were identified in initial high-grade gliomas and recurrent gliomas treated by chemoradiotherapy: Isocitrate dehydrogenase 1/2 (IDH1/2) mutation, epidermal growth factor receptor variant III (EGFRvIII) mutation, tumor protein P53 mutation, PTEN mutation, O6-methylguanine-DNA methyltransferase promoter methylation and telomerase reverse transcriptase (TERT) mutation. The expression profile of 58 receptor tyrosine kinases (RTKs) were also examined. It was revealed that the proneural tumor subtype and IDH1/2 mutation are more frequent in recurrent tumors compared with initial tumors. Lower frequencies of the classical subtype, EGFRvIII mutation and TERT mutation were identified in recurrent tumors. A set of six RTK genes in which the level of expression was influenced by chemoradiotherapy was identified. Survival analysis revealed that the expression of several RTKs, including apoptosis-associated tyrosine kinase, fibroblast growth factor receptor 1 and insulin-like growth factor 1 receptor (IGF1R), was associated with patient survival. The stimulation of glioma cells by IGF1 in vitro was found to decreased the viability of the cells following treatment with temozolomide (TMZ). In addition, the expression level of IGF1R was increased in glioma cells treated with TMZ. These data suggest that altered RTK expression levels may influence the sensitivity of glioma to chemoradiotherapy. © 2019 Spandidos Publications. All rights reserved.

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出版当年[2018]版:
大类 | 4 区 医学
小类 | 4 区 肿瘤学
最新[2023]版:
大类 | 4 区 医学
小类 | 4 区 肿瘤学
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出版当年[2017]版:
Q4 ONCOLOGY
最新[2023]版:
Q3 ONCOLOGY

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