Advanced WHO Grade Research Articles

ARID4B is a good biomarker to predict tumour behaviour and decide WHO grades in gliomas and meningiomas

AimsAlthough ARID4B is known to promote tumour metastasis in breast cancer and inhibit transformation and progression in leukaemia, the possible effect of ARID4B on primary brain tumours (PBTs) is not...

Expression of CPEB4 in Human Glioma and Its Correlations With Prognosis.

CPEB4 plays an important role in cancer progression. However, the clinicopathological significance of CPEB4 expression to glioma and its expression levels in glioma tissues and cell lines are unknown. The present study investigated the potential prognostic value of CPEB4 for human glioma.Immunohistochemistry (IHC) was performed to examine the dynamics of CPEB4 expression in glioma and nonneoplastic brain tissues, and the expression of CPEB4 in cell lines and freshly prepared tissue samples was measured using Western blotting and real-time PCR.CPEB4 was highly expressed at the mRNA and protein levels in 4 glioma cell lines and in 4 freshly prepared glioma tissues. Immunohistochemical analysis demonstrated that CPEB4 expression in glioma tissue was higher than that in corresponding nonneoplastic brain tissue (P < 0.01). This high expression level was further increased in high-grade gliomas, and the CPEB4 expression level correlated with the WHO classification (r = 0.774, P < 0.01). Moreover, the overall survival of glioma patients displaying high CPEB4 protein expression (P < 0.01) was clearly lower than that of those displaying low CPEB4 expression, and the high CPEB4 expression indicated a poorer survival in high-grade glioma patients (P < 0.01).Our study suggests that CPEB4 is significantly expressed in human glioma and that the upregulation of CPEB4 protein is significantly associated with advanced WHO grade. CPEB4 may serve as a highly sensitive prognostic indicator for glioma patients.

Expression of microRNA-218 and its clinicopathological and prognostic significance in human glioma cases.

MicroRNAs are a class of noncoding RNAs which regulate multiple cellular processes during tumor development. The purpose of this report is to investigate the clinicopathological and prognostic significance of miR-218 in human gliomas. Quantitative RT-PCR (qRT-PCR) was conducted to detect the expression of miR-218 in primary normal human astrocytes, three glioma cell lines and 98 paired glioma and adjacent normal brain tissues.Associations of miR-218 with clinicopathological variables of glioma patients were statistically analyzed. Finally, a survival analysis was performed using the Kaplan-Meier method and Cox's proportional hazards model. The expression level of miR-218 in primary normal human astrocytes was significantly higher than that in glioma cell lines (p<0.01). Also, the expression level of miR-218 in glioma tissues was significantly downregulated in comparison with that in the adjacent normal brain tissues (p<0.001). Statistical analyses demonstrated that low miR-218 expression was closely associated with advanced WHO grade (p=0.002) and low Karnofsky performance score (p=0.010) of glioma patients. Kaplan-Meier analysis with the log-rank test showed that patients with low-miR-218 expression had poorer disease-free survival and overall survival (p=0.0045 and 0.0124, respectively). Multivariate analysis revealed that miR-218 expression was independently associated with the disease-free survival (p=0.009) and overall survival (p=0.004) of glioma patients. Our results indicate that miR-218 is downregulated in gliomas and that its status might be a potential valuable biomarker for glioma patients.

Up-regulated oncoprotein P28GANK correlates with proliferation and poor prognosis of human glioma

BackgroundThe significance of p28GANK in gliomas remains unknown. This study aims to clarify the clinical significance of p28GANK in human gliomas.MethodsThe expression of p28GANK in 138 gliomas and 50 matched para-cancerous tissues was detected by immunohistochemical staining, and statistical analyses were performed to test the correlation of p28GANK with clinical parameters. To investigate the effects of p28GANK down-regulation on the growth of cells both in vitro and in vivo, an siRNA targeting p28GANK was transfected into U251 cells.ResultsP28GANK expression was significantly higher in tumor specimens than in matched para-cancerous tissues. Over-expressed p28GANK significantly correlated with high karnofsky performance score (KPS), advanced WHO grade and poor overall survival of the patients. Univariate analysis showed that WHO grade and KPS also correlated with the survival of patients, and multivariate analysis suggested that KPS and p28GANK expression were two independent prognostic factors. Moreover, p28GANK gene silencing decreased the malignant growth of U251 cells both in vitro and in vivo.ConclusionsIncreased expression of p28GANK is correlated with poor clinical outcomes in glioma patients. The down-regulation of p28GANK significantly inhibited cell proliferation, indicating that p28GANK might be a potential therapeutic target for glioma treatment.

Co-expression of MMP-14 and MMP-19 predicts poor survival in human glioma

Matrix metalloproteinase (MMP)-14 and MMP-19 have been demonstrated to play an important role in the development of human gliomas. However, their prognostic values are not clear. The aim of this study was to investigate whether co-expression of MMP-14 and MMP-19 has prognostic relevance in human gliomas. Immunohistochemistry and western blot were used to investigate the expression of MMP-14 and MMP-19 proteins in 128 patients with gliomas. The expression levels of MMP-14 and MMP-19 proteins in glioma tissues were both significantly higher (both P < 0.001) than those in non-neoplastic brain tissues according to the immunohistochemistry analysis, which was confirmed by the western blot analysis. Additionally, the overexpression of either MMP-14 or MMP-19 was significantly associated with the advanced WHO grade (both P = 0.02), the low Karnofsky performance score (KPS) (P = 0.008 and 0.01, respectively) and the poor overall survival (both P = 0.01). Moreover, the Multivariate Cox proportional-hazards regression analysis revealed that the increased expressions of MMP-14 and MMP-19 were both independent prognostic factors for poor overall survival (both P = 0.02). Furthermore, the co-expression of MMP-14 and MMP-19 was additively and more significantly (P = 0.006) associated with adverse prognosis in patients with gliomas than respective expression of MMP-14 and MMP-19. These findings indicated for the first time that the co-expression of MMP-14 and MMP-19 is significantly correlated with prognosis in glioma patients, suggesting that the co-expression of these proteins may be used as both an early diagnostic and independent prognostic marker.

Oncogenic role of SOX9 expression in human malignant glioma

SOX9 belongs to the SOX (Sry-related high-mobility group box) family and acts as a transcription factor that plays a central role in the development and differentiation of multiple cell lineages. Recent studies have demonstrated that SOX9 is required for the carcinogenesis in several cancer types. The aim of this study was to investigate the clinicopathological significance of SOX9 expression in human malignant glioma. SOX9 mRNA expression was detected by real-time quantitative RT-PCR assay in glioma and nonneoplastic brain tissues. Then, the association of SOX9 mRNA expression with clinicopathological factors or prognosis of glioma patients was statistically analyzed. In addition, the small interfering RNA was used to knockdown SOX9 expression in a glioma cell line and to analyze the effects of SOX9 inhibition on cell growth, cell cycle and apoptosis of glioma cell line. The expression level of SOX9 mRNA in glioma tissues was significantly higher than that in corresponding nonneoplastic brain tissues (P < 0.001). In addition, a high level of SOX9 mRNA expression was significantly more common in glioma tissues with advanced WHO grade than those with low grade (P = 0.02). The increased expression of SOX9 mRNA was also significantly correlated with low Karnofsky performance score (P = 0.008). Meanwhile, the disease-free and overall survival rates of patients with high SOX9 mRNA expression were obviously lower than those of patients with low SOX9 mRNA expression (both P = 0.01). Multivariate analysis showed that high SOX9 mRNA expression was an independent prognostic factor for glioma patients (P = 0.02). Moreover, the down-regulation of SOX9 could inhibit the cell growth, induce the cell arrest in G2/M phase of cell cycle and enhance the apoptosis in glioma cells. Our data suggest for the first time that the over-expression of SOX9 mRNA is closely associated with poor clinical outcome of patients with malignant gliomas, and targeting SOX9 may be a novel therapeutic strategy for this tumor.