title: Overexpression of ubiquitin-specific protease 2a (USP2a) and nuclear factor erythroid 2-related factor 2 (Nrf2) in human gliomas.
abstract: BACKGROUND
  Gliomas are among the most frequent adult primary brain tumors. Recent studies have shown that there are novel opportunities for developing therapeutics by targeting the differentiation and self-renewal features of glioma.
  
  
  OBJECTIVE
  The aim of this study was to evaluate the expression levels of USP2a an Nrf2 in patients with glioma and their association with prognosis of gliomas that was detected with immunohistochemical staining.
  
  
  METHODS
  In this study, 40 patient's tissue samples with primary gliomas were collected between January 2009 and December 2013. MRI of patients was done before and within 24 h after surgery. USP2a and Nrf2 expression levels were examined by immunohistochemistry. Data were analyzed using the SPSS 16.0, X(2) test, log-rank test and Kaplan-Meier method.
  
  
  RESULTS
  Immunohistochemistry indicated that USP2a expression was increased in glioma cells than normal brain tissues. The increased USP2a staining was markedly correlated with advanced tumor grade (P=0.02) and age (P=0.016). Our result showed that Nrf2 expression was significantly higher in glioma cells as compared to normal brain tissues. The high expression level of Nrf2 was markedly linked to age (P=0.007), and tumor grade (P=0.03). Kaplan-Meier survival and log-rank analysis indicated that patients with low expression of USP2a had longer overall survival than those with high levels (log-rank test P<0.001). Moreover, patients with high Nrf2 expression had shorter overall survival than those with low levels (log-rank test P<0.001). In the univariate analysis, the high expression of Nrf2 and USP2a (P=0.004; P=0.006), age (P=0.025), and tumor grade (P=0.001) were correlated with poor survival. Multivariate Cox proportional hazards model indicated that, high Nrf2 and USP2a staining (P=0.001; P=0.003), advanced tumor grade (P=0.01) and age (P=0.033) were independent predictor of overall survival.
  
  
  CONCLUSIONS
  In summary, the result of this study showed USP2a and Nrf2 may be as prognostic marker in patients with gliomas.
authors.affiliation: Department of Neurosurgery, AJA University of Medical Sciences, Tehran, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Boustani
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: General Medicine, Tehran Medical Science Branch, Islamic Azad University, Tehran, Iran.
authors.forename: Fermoozan
authors.initials: F
authors.lastname: Nikpasand
authors.affiliation: Department of Emergency Medicine, Alborz University of Medical Sciences, Karaj, Iran.
authors.forename: Zabihollah
authors.initials: Z
authors.lastname: Taleshi
authors.affiliation: Department of Emergency Medicine, Alborz University of Medical Sciences, Karaj, Iran.
authors.forename: Koorosh
authors.initials: K
authors.lastname: Ahmadi
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, 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; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010450:Endopeptidases / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis* / Q000235:genetics; D043222:Ubiquitin Thiolesterase
chemical_list: D014408:Biomarkers, Tumor; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D010450:Endopeptidases; C108665:USP2 protein, human; D043222:Ubiquitin Thiolesterase
keywords: Gliomas; Immunohistochemistry; Nrf2; Patient; Prognosis; USP2a