title: Reduced expression of SMAD4 in gliomas correlates with progression and survival of patients.
abstract: BACKGROUND
  To examine the expression of SMAD4 at gene and protein levels in glioma samples with different WHO grades and its association with survival.
  
  
  METHODS
  Two hundreds fifty-two glioma specimens and 42 normal control tissues were collected. Immunochemistry assay, quantitative real-time PCR and Western blot analysis were carried out to investigate the expression of SMAD4. Kaplan-Meier method and Cox's proportional hazards model were used in survival analysis.
  
  
  RESULTS
  Immunohistochemistry showed that SMAD4 expression was decreased in glioma. SMAD4 mRNA and protein levels were both lower in glioma compared to control on real-time PCR and Western blot analysis (both P < 0.001). In addition, its expression levels decrease from grade I to grade IV glioma according to the results of real-time PCR, immunohistochemistry analysis and Western blot. Moreover, the survival rate of SMAD4-positive patients was higher than that of SMAD4-negative patients. We further confirmed that the loss of SMAD4 was a significant and independent prognostic indicator in glioma by multivariate analysis.
  
  
  CONCLUSIONS
  Our data provides convincing evidence for the first time that the reduced expression of SMAD4 at gene and protein levels is correlated with poor outcome in patients with glioma. SMAD4 may play an inhibitive role during the development of glioma and may be a potential prognosis predictor of glioma.
authors.affiliation: Department of Neurosurgery, Institute for functional neurosurgery P.L.A, TangDu Hospital, Fourth Military Medical University, Xi'an, 710038, PR China.
authors.forename: Shi-ming
authors.initials: SM
authors.lastname: He
authors.forename: Zhen-wei
authors.initials: ZW
authors.lastname: Zhao
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Ji-pei
authors.initials: JP
authors.lastname: Zhao
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Fang
authors.initials: F
authors.lastname: Hou
authors.forename: Guo-dong
authors.initials: GD
authors.lastname: Gao
mesh_terms: D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D051901:Smad4 Protein / Q000096:biosynthesis* / Q000235:genetics; D015996:Survival Rate
chemical_list: C497796:SMAD4 protein, human; D051901:Smad4 Protein