title: Somatic CPEB4 and CPEB1 genes mutations spectrum on the prognostic predictive accuracy in patients with high-grade glioma and their clinical significance.
abstract: BACKGROUND
  Glioblastoma (grade IV glioma/GBM) is characterized by extremely aggressive invasion and proliferative nature.
  
  
  OBJECTIVE
  The main goal of this study was to evaluate the expression patterns of CPEB1 and CPEB4 in glioma patients.
  
  
  METHODS
  41 paraffin-embedded tissue samples with glioma (WHO I-IV) were collected between January 2008 and December 2012 in Tehran, Iran. MRI of patients was done before and within 24 h after surgery and gliomas investigated using quantitative real-time PCR and immunohistochemistry. Kaplan-Meier survival and Cox regression were applied to assess the prognosis of patients.
  
  
  RESULTS
  The mRNA level of CPEB4 was strongly increased in tumor tissues (0.67±3.154 vs. 1.671±0.51; P=0.001). Furthermore, CPEB1 mRNA was significantly decreased in tumor tissues compared to normal tissues (2.852±0.587 vs. 1.471±0.862; P=0.025). Our findings showed that CPEB4 levels was markedly increased in patients with advanced grade gliomas (P=0.003). In addition, CPEB1 mRNA levels were not associated with clinicopathological features. Of the 41 cases, high CPEB4 expression was found in 29 patients (70.73%), while 12 cases (29.26%) showed weak expression levels, while the protein expression of CPEB4 were remarkably weak in normal tissues (P=0.001). However, no correlation was found between expression levels of CPEB1 and clinicopathological characteristics. Kaplan-Meier survival and log-rank test indicated that high expression of CPEB4 was correlated with shorter overall survival (log-rank test P<0.001). Furthermore, low expression of CPEB1 was linked to shorter overall survival (log-rank test P=0.021). Multivariate Cox proportional hazards model showed that high CPEB1 (P=0.027), low CPEB4 expressions (P=0.021), and advanced tumor grade (P=0.036) were independent predictor of overall survival.
  
  
  CONCLUSIONS
  Our data indicated expressions levels of CPEB4 and CPEB1 are correlated with overall survival in patients with glioma.
authors.affiliation: Department of Nuerosurgery, AJA University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Boustani
authors.affiliation: Department of Neurology, AJA University of Medical Sciences, Tehran, Iran.
authors.forename: Farzad
authors.initials: F
authors.lastname: Mehrabi
authors.affiliation: Department of Molecular Biology, Baqiyatallah University of Medical Sciences, Tehran, Iran.
authors.forename: Emad
authors.initials: E
authors.lastname: Yahaghi
authors.affiliation: Department of Neurosurgery, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Reza Jalili
authors.initials: RJ
authors.lastname: Khoshnood
authors.affiliation: Department of Neurosurgery, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammadreza
authors.initials: M
authors.lastname: Shahmohammadi
authors.affiliation: Young Researchers and Elite Club, North Tehran Branch, Islamic Azad University, Tehran, Iran.
authors.forename: Ebrahim Khodaveri
authors.initials: EK
authors.lastname: Darian
authors.affiliation: Department of Nuerosurgery, AJA University of Medical Sciences, Tehran, Iran. Electronic address: Pedram_kg@yahoo.com.
authors.forename: Peyman Karimi
authors.initials: PK
authors.lastname: Goudarzi
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011237:Predictive Value of Tests; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000235:genetics*; D015996:Survival Rate / Q000639:trends; D014157:Transcription Factors / Q000235:genetics*; D039221:mRNA Cleavage and Polyadenylation Factors / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C490386:CPEB1 protein, human; C554939:CPEB4 protein, human; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D039221:mRNA Cleavage and Polyadenylation Factors
keywords: Analysis; Biomarker; Glioma; IHC; PCR; Patient; Survival