Reduced expression of SMAD4 in gliomas correlates with progression and survival of patients

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.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.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.Human gliomas are the most common primary intracranial tumors in adults. 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. However, these approaches do not benefit all patients equally. Adverse effects of these approaches even dramatically deteriorate the quality-of-life of some patients. Therefore, individualized therapy should be considered as a valuable approach for patients with high-grade gliomas. Molecular profiling of gliomas may define the critical genetic alterations that underlie