FGFR3, as a receptor tyrosine kinase, is associated with differentiated biological functions and improved survival of glioma patients
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Zheng Wang1,2,6, Chuanbao Zhang1,2,6, Lihua Sun1,6, Jingshan Liang1,6, Xing Liu1,2,6, Guanzhang Li1,2,6, Kun Yao3,6, Wei Zhang2,4,5,6, Tao Jiang1,2,4,5,6
1Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
2Beijing Tiantan Hospital, Capital Medical University, Beijing, China
3Sanbo Brain Hospital, Capital Medical University, Beijing, China
4Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, China
5China National Clinical Research Center for Neurological Diseases, Beijing, China
6Chinese Glioma Genome Atlas network (CGGA), Beijing, China
Tao Jiang, email: [email protected]
Keywords: FGFR3, receptor tyrosine kinase, FGFR-TACC fusion genes, glioma
Received: March 21, 2016 Accepted: October 26, 2016 Published: November 05, 2016
Background: Activation of receptor tyrosine kinases is common in Malignancies. FGFR3 fusion with TACC3 has been reported to have transforming effects in primary glioblastoma and display oncogenic activity in vitro and in vivo. We set out to investigate the role of FGFR3 in glioma through transcriptomic analysis.
Results: FGFR3 increased in Classical subtype and Neural subtype consistently in CGGA and TCGA cohort. Similar patterns of FGFR3 distribution through subtypes were observed in CGGA and TCGA samples. Gene ontology analysis was performed with genes that were significantly correlated with FGFR3 expression. We found that positively associated biological processes of FGFR3 were focused on differentiated cellular functions and neuronal activities, while negatively correlated biological processes focused on mitosis and cell cycle phase. Clinical investigation showed that higher FGFR3 expression predicted improved survival for glioma patients, especially in Proneural subtype. Moreover, FGFR3 showed very limited relevance with other receptor tyrosine kinases in glioma at transcriptome level.
Materials and Methods: FGFR3 expression data of glioma was obtained from Chinese Glioma Genome Atlas (CGGA) and TCGA (The Cancer Genome Atlas). In total, RNA sequencing data of 325 glioma samples and mRNA microarray data of 301 samples from CGGA dataset were enrolled into this study. To consolidate the findings that we have revealed in CGGA dataset, RNA-seq data of 672 glioma samples from TCGA dataset were used as a validation cohort. R language was used as the main tool to perform statistical analysis and graphical work.
Conclusions: FGFR3 expression increased in classical and neural subtypes and was associated with differentiated cellular functions. FGFR3 showed very limited correlation with other common receptor tyrosine kinases, and predicted improved survival for glioma patients.
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