title: Differential Expression of Circular RNAs in Glioblastoma Multiforme and Its Correlation with Prognosis.
abstract: OBJECTIVE
  The present study aimed to explore the expression profiles of circular RNAs (circRNAs) in glioblastoma multiforme (GBM) in an attempt to identify potential core genes in the pathogenesis of this tumor.
  
  
  METHODS
  Differentially expressed circRNAs were screened between tumor tissues from five GBM patients and five normal brain samples using Illumina Hiseq. Bioinformatics analysis was used to analyze their potential function. CircBRAF was further detected in different WHO grades glioma tissues and normal brain tissues. Kaplan-Meier curves and multivariate Cox's analysis were used to analyze the association between circBRAF expression level and prognosis of glioma patients.
  
  
  RESULTS
  A total of 1411 differentially expressed circRNAs were identified in GBM patients including 206 upregulated circRNAs and 1205 downregulated circRNAs. Differential expression of circRNAs was closely associated with the biological process and molecular function. The downregulated circRNAs were mainly associated with ErbB and Neurotrophin signaling pathways. Moreover, the expression level of circBRAF in normal brain tissues was significantly higher than that in glioma tissues (P<.001). CircBRAF was significantly lower in glioma patients with high pathological grade (WHO III & IV) than those with low grade (WHO I & II) (P<.001). Cox analysis revealed that high circBRAF expression was an independent biomarker for predicting good progression-free survival and overall survival in glioma patients (HR=0.413, 95% CI 0.201-0.849; HR=0.299, 95% CI 0.135-0.661; respectively).
  
  
  CONCLUSIONS
  The present study identified a profile of dysregulated circRNAs in GBM. Bioinformatics analysis showed that dysregulated circRNAs might be associated with tumorigenesis and development of GBM. In addition, circBRAF could severe as a biomarker for predicting pathological grade and prognosis in glioma patients.
authors.affiliation: Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China.
authors.forename: Junle
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China; Department of Neurosurgery, No. 98 Hospital of Chinese People's Liberation Army, Huzhou 313000, China.
authors.forename: Jingliang
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Emergency, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Xia
authors.affiliation: Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China.
authors.forename: Hongkang
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of spinal surgery, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Wan
authors.affiliation: Department of Reproductive Medical Center, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Sheng
authors.affiliation: Department of Reproductive Medical Center, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Reproductive Medical Center, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China. Electronic address: qianjun19@126.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Qian
authors.affiliation: Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China. Electronic address: boyluochun@126.com.
authors.forename: Chun
authors.initials: C
authors.lastname: Luo