FGFR3, as a receptor tyrosine kinase, is associated with differentiated biological functions and improved survival of glioma patients.
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.


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.
Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.|Beijing Tiantan Hospital, Capital Medical University, Beijing, China.|Chinese Glioma Genome Atlas network (CGGA), Beijing, China.
Zheng
Z
Wang
Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.|Beijing Tiantan Hospital, Capital Medical University, Beijing, China.|Chinese Glioma Genome Atlas network (CGGA), Beijing, China.
Chuanbao
C
Zhang
Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.|Chinese Glioma Genome Atlas network (CGGA), Beijing, China.
Lihua
L
Sun
Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.|Chinese Glioma Genome Atlas network (CGGA), Beijing, China.
Jingshan
J
Liang
Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.|Beijing Tiantan Hospital, Capital Medical University, Beijing, China.|Chinese Glioma Genome Atlas network (CGGA), Beijing, China.
Xing
X
Liu
Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.|Beijing Tiantan Hospital, Capital Medical University, Beijing, China.|Chinese Glioma Genome Atlas network (CGGA), Beijing, China.
Guanzhang
G
Li
Sanbo Brain Hospital, Capital Medical University, Beijing, China.|Chinese Glioma Genome Atlas network (CGGA), Beijing, China.
Kun
K
Yao
Beijing Tiantan Hospital, Capital Medical University, Beijing, China.|Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, China.|China National Clinical Research Center for Neurological Diseases, Beijing, China.|Chinese Glioma Genome Atlas network (CGGA), Beijing, China.
Wei
W
Zhang
Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.|Beijing Tiantan Hospital, Capital Medical University, Beijing, China.|Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, China.|China National Clinical Research Center for Neurological Diseases, Beijing, China.|Chinese Glioma Genome Atlas network (CGGA), Beijing, China.
Tao
T
Jiang
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015331:Cohort Studies; D015972:Gene Expression Regulation, Neoplastic; D063990:Gene Ontology; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D016019:Survival Analysis; D059467:Transcriptome; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D008869:Microtubule-Associated Proteins; D015514:Oncogene Proteins, Fusion; C120551:TACC3 protein, human; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3
FGFR-TACC fusion genes; FGFR3; glioma; receptor tyrosine kinase