ABSTRACT
To investigate whether Jun activation domain-binding protein 1 (Jab1) expression is correlated with p27 protein and its phosphorylation status as well as how it might be clinically relevant in glioma, we carried out an immunohistochemical study of Jab1, Ser10-phosphorylated p27 (pSer10p27), and p27 using biopsies from 192 patients with primary glioma. Kaplan-Meier survival and Cox regression analyses were performed to evaluate the prognosis of patients. Immunostaining revealed a positive correlation between Jab1 and cytoplasmic p27 as well as pSer10p27 in all glioma cases. In addition, patients displaying the overexpression of Jab1, cytoplasmic p27, and pSer10p27 were significantly associated with unfavorable clinicopathological variables. Statistical analysis showed that patients expressing Jab1, cytoplasmic p27, and pSer10p27 have poor overall survival rates relative to those not expressing these proteins. Cox multifactor analysis showed that Jab1 (P = 0.006), cytoplasmic p27 (P = 0.01), and pSer10p27 (P = 0.009) were independent prognosis factors for human glioma. In conclusion, the current results showed convincing evidence that the overexpression of Jab1, cytoplasmic p27, and pSer10p27 proteins is correlated with poor outcome in patients with glioma and that these three proteins may be useful markers to predict the prognosis of this tumor.
Subject(s)
Brain Neoplasms/metabolism , Glioma/metabolism , Peptide Hydrolases/biosynthesis , Proliferating Cell Nuclear Antigen/biosynthesis , Adult , Biomarkers, Tumor/analysis , Brain Neoplasms/mortality , COP9 Signalosome Complex , Female , Glioma/mortality , Humans , Immunohistochemistry , Intracellular Signaling Peptides and Proteins/analysis , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Grading , Peptide Hydrolases/analysis , Phosphorylation , Prognosis , Proliferating Cell Nuclear Antigen/analysis , Proportional Hazards ModelsABSTRACT
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.
