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Updated: Jan 2, 2026
Translational Orthotopic Models of Glioblastoma Multiforme
Published on: February 17, 2023
Receptor tyrosine kinase expression in high-grade gliomas before and after chemoradiotherapy
Kuanyu Wang1,2, Ruoyu Huang2, Chenxing Wu3
1Department of Gamma Knife Center, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, P.R. China.
Abstract:
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.
Insights
This study reveals that specific receptor tyrosine kinase (RTK) expression changes in glioma impact chemoradiotherapy response and patient survival. Altered RTK levels, particularly IGF1R, may affect treatment sensitivity in malignant brain tumors.
Area of Science:
- Neuro-oncology
- Cancer Genomics
- Molecular Biology
Background:
- Glioma, a common malignant brain tumor, exhibits invasive growth and resistance to chemoradiotherapy.
- Key molecular subtypes identified include IDH1/2, EGFRvIII, TP53, PTEN, MGMT promoter methylation, and TERT mutations.
- Understanding these subtypes and their response to therapy is crucial for improving patient outcomes.
Purpose of the Study:
- To investigate the molecular subtypes and receptor tyrosine kinase (RTK) expression profiles in initial and recurrent high-grade gliomas.
- To determine the influence of chemoradiotherapy on RTK expression levels.
- To correlate RTK expression with patient survival and temozolomide (TMZ) sensitivity.
Main Methods:
- Analysis of Cancer Genome Atlas (TCGA) mutation subtypes in glioma.
- Examination of the expression profile of 58 receptor tyrosine kinases (RTKs).
- Survival analysis and in vitro studies using glioma cell lines treated with IGF1 and TMZ.
Main Results:
- Recurrent gliomas showed a higher frequency of proneural subtype and IDH1/2 mutations, with lower frequencies of classical subtype, EGFRvIII, and TERT mutations compared to initial tumors.
- Six RTK genes were identified whose expression levels were altered by chemoradiotherapy.
- Expression of specific RTKs, including IGF1R, correlated with patient survival, and IGF1 stimulation decreased TMZ-induced glioma cell viability.
Conclusions:
- Altered RTK expression is a significant factor influencing glioma sensitivity to chemoradiotherapy.
- Specific RTKs, such as IGF1R, represent potential therapeutic targets for overcoming treatment resistance.
- Molecular profiling of glioma subtypes and RTK expression is essential for personalized treatment strategies.
