Prognostic significance of CD147 in patients with glioblastoma.

CD147, also known as extracellular matrix metalloproteinase inducer, is a widely distributed cell surface glycoprotein that belongs to the immunoglobulin superfamily. CD147 has been proved to be enriched on the surface of many tumor cells, promoting tumor growth, invasion and metastasis by its stimulation effect on adjacent fibroblasts to produce matrix metalloproteinases. In this study, we aimed to explore the expression pattern of CD147 in glioblastoma (GBM) and investigate whether it could be used to assess subsequent prognosis of patients. For that, we recruited a total of 206 patients with pathologically confirmed GBM and 36 normal control brain tissue specimens. The expression of CD147 in GBM and normal tissues was investigated by immunohistochemistry assay. Genetic factors including MGMT and IDH1 mutation were also investigated to justify the prognostic significance of CD147. Results showed that CD147 expression was increased in GBM compared with that in normal tissues. Kaplan-Meier analysis showed that increased CD147 expression was associated with poor overall survival of patients with GBM. Moreover, Cox's proportional hazards model revealed that CD147 expression was an independent and significant prognostic marker of overall survival in GBM patients. These results proved that CD147 expression was relatively abundant in GBM and can be potentially used to predict prognosis and treatment response in GBM patients.

Downregulation of chromatin remodeling factor CHD5 is associated with a poor prognosis in human glioma.

Chromodomain helicase DNA-binding protein 5 (CHD5), a member of the CHD family, is involved in key cellular processes including chromatin remodeling, cell cycle regulation, and cellular adhesion. Recent studies have demonstrated that CHD5 is the product of a novel tumor suppressor gene and is implicated in certain tumor types. However, the clinicopathological significance of CHD5 expression in human malignant gliomas remains unclear. To address this problem, CHD5 expression in human gliomas and non-neoplastic brain tissues was measured using real-time quantitative polymerase chain reaction (RT-PCR) assay, Western blot, and immunohistochemistry. The association of CHD5 immunostaining with clinicopathological factors or prognosis of glioma patients was statistically analyzed. Genetic and protein expression of CHD5 were downregulated in glioma tissues compared to corresponding non-neoplastic brain tissues (both p<0.001). Additionally, decreased expression of CHD5 in glioma was significantly associated with pathological grade (p=0.007); high pathological grade was associated with low CHD5 expression. Loss of CHD5 protein expression was also significantly correlated with a low Karnofsky performance scale score (p=0.01). Moreover, overall survival of patients with low CHD5 protein expression was dramatically shorter than those of patients with high CHD5 protein expression (p=0.003). Multivariate Cox regression analysis indicated that CHD5 expression was an independent prognostic factor for patients with gliomas (p=0.01). In conclusion, these data offer convincing evidence for the first time that CHD5 might act as a tumor suppressor in glioma, may act as a regulator of aggressive development, and is a candidate prognostic marker for this malignancy.

Matrix metalloproteinase-9 expression is increased in astrocytic glioma and associated with prognosis of patients.

OBJECTIVE: Glioma is the most common type of primary central nervous system tumor. This study was aimed at investigating the expression of matrix metalloproteinase-9 in astrocytic glioma samples and its association with clinicopathological characteristics as well as survival of patients. METHODS: Astrocytic glioma samples from 272 patients who had not received chemotherapy or radiotherapy were collected, in which matrix metalloproteinase-9 expression was assessed by immunochemistry assays. The association of staining evaluation results with clinicopathological characteristics was analyzed by appropriate statistical analysis. Kaplan-Meier analysis and Cox proportional hazards regression models were used to investigate the association between matrix metalloproteinase-9 expression and survival of patients. RESULTS: Results showed that matrix metalloproteinase-9 expression is increased in astrocytic glioma and associated with tumor progression as its expression increased from Grade II to Grade IV glioma (P<0.001). Kaplan-Meier analysis showed that patients with glioma with higher matrix metalloproteinase-9 expression tend to have shorter overall survival time (P<0.001). In multivariate analysis, matrix metalloproteinase-9 expression was proved to be an independent prognostic factor for patients with astrocytic glioma (P<0.001). CONCLUSIONS: This study confirmed the overexpression of matrix metalloproteinase-9 and its association with tumor progression in astrocytic glioma. It also provided the first evidence that matrix metalloproteinase-9 expression in glioma was an independent prognostic factor of patients, which might be a potential diagnostic and therapeutic target of astrocytic glioma.

Elevated expression of chloride intracellular channel 1 is correlated with poor prognosis in human gliomas.

BACKGROUND: Chloride intracellular channel 1 (CLIC1) is expressed ubiquitously in human tissues and is involved in the regulation of cell cycle, cell proliferation and differentiation. Recent studies have shown that CLIC1 is highly expressed in several human malignant tumors. However, its roles in human gliomas are still unclear. The aim of this study was to investigate the clinicopathological significance and prognostic value of CLIC1 expression in human gliomas. METHODS: CLIC1 expression in human gliomas and nonneoplastic brain tissues was measured by real-time quantitative RT-PCR assay and immunohistochemistry. Its association with clinicopathological factors or prognosis in patients with gliomas was statistically analyzed. RESULTS: The expression of CLIC1 at both mRNA and protein levels was significantly increased in high-grade (Grade III~IV) glioma tissues compared with that in low-grade (Grade I~II) and nonneoplastic brain tissues, and was up-regulated with ascending tumor World Health Organization (WHO) grades. The elevated expression of CLIC1 protein was also significantly correlated with low Karnofsky performance score (KPS) (P=0.008). Moreover, both univariate and multivariate analysis shown that high CLIC1 expression was significantly associated with poor prognosis in patients with gliomas (P<0.001 and P=0.01, respectively). In particular, the elevated CLIC1 expression also correlated with shorter overall survival in different glioma subgroups stratified according to the WHO grading. CONCLUSIONS: Our data provide the first evidence that CLIC1 expression might play an important role in the regulation of aggressiveness in human gliomas. The elevated expression of CLIC1 might represent a valuable prognostic marker for this disease.

Potential role of Jun activation domain-binding protein 1 and phosphorylated p27 expression in prognosis of glioma.

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.

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

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.