Abstract
BackgroundTo examine the expression of SMAD4 at gene and protein levels in glioma samples with different WHO grades and its association with survival.MethodsTwo 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.ResultsImmunohistochemistry 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.ConclusionsOur 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.
Highlights
Human gliomas are the most common primary intracranial tumors in adults
3.1 SMAD4 protein levels in glioma tissues by immunohistochemistry assay and survival analysis SMAD4 expression was studied in a total of 252 glioma specimens of which 113 were low grade glioma and 139 were high grade
We found a significant decrease of SMAD4 expression in glioma compared with normal brain tissues (P < 0.001)
Summary
A grading scheme proposed by the WHO distinguishes four different grades of gliomas, of which glioblastoma multiforme (GBM) WHO grade IV is the most malignant variant with a median survival time of 1 year [1]. Many aggressive treatment approaches, such as postoperative radiation therapy and chemotherapy, have been used clinically. These approaches do not benefit all patients . Adverse effects of these approaches even dramatically deteriorate the quality-of-life of some patients. Individualized therapy should be considered as a valuable approach for patients with high-grade gliomas. To examine the expression of SMAD4 at gene and protein levels in glioma samples with different WHO grades and its association with survival
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