Project description:Combing WHO classification and molecular characteristics to analysis gliomas more and more important. But Grade III glioma samples have a big difference within the group had not been reported as far as we know. In this study, we proposed a model to evaluate diagnosis and prognosis of Grade III glioma patients, and two independent datasets indicated that the model has a good predictive ability. Therefore, this strategy provides a new method to assist diagnosis and treatment of Grade III glioma patients.
Project description:Glioma tumors arise from normal glial cells (astrocytes). Gliomas are morphologically and clinically classified into four malignancy grades as Grade I, II, III and IV. Grade I and II comprise low grade gliomas that grow slowly, are well differentiated and have a better prognosis and survival compared to grades III and IV. In contrast, grade III-IV lack endothelial proliferation and are highly vascular with a tendency to infiltrate and have areas of extensive necrosis and hypoxia. In the present study, we used iTRAQ (isobaric tags for relative and absolute quantitation) - based quantitative proteomic approach followed by online liquid chromatography and high resolution tandem mass spectrometry (LC-MS/MS) to identify differential nuclear proteins enriched with transcriptional regulatory function from three different grades of astrocytoma tumors (WHO Grade II, III and IV) compared to control.
Project description:High-grade glioma is highly aggressive and malignant, resistant to combined therapies and easy to relapse. A better understanding of circRNA biological function in high-grade glioma might contribute to the therapeutic efficacy. Here, a circRNA merely up-regulated in high-grade glioma, circGLIS3 (hsa_circ_0002874, originating from exon 2 of GLIS3), was validated by microarray and qRT-PCR. Functional experiments uncovered that up-regulation of circGLIS3 promoted glioma cell migration and invasion, and showed aggressive characteristics in tumor-bearing mice. Fluorescence in situ hybridization, RNA pull-down, RNA immunoprecipitation and immunohistochemical staining showed that circGLIS3 could promoted Ezrin T567 phosphorylation. Further investigation showed that circGLIS3 could be excreted by glioma through exosomes and induced endothelial cells angiogenesis. This study indicates that circGLIS3 is up-regulated in high-grade glioma and contributes to the invasion and angiogenesis of glioma via promoting Ezrin T567 phosphorylation.
Project description:High-grade glioma is highly aggressive and malignant, resistant to combined therapies and easy to relapse. A better understanding of circRNA biological function in high-grade glioma might contribute to the therapeutic efficacy. Here, a circRNA merely up-regulated in high-grade glioma, circGLIS3 (hsa_circ_0002874, originating from exon 2 of GLIS3), was validated by microarray and qRT-PCR. Functional experiments uncovered that up-regulation of circGLIS3 promoted glioma cell migration and invasion, and showed aggressive characteristics in tumor-bearing mice. Fluorescence in situ hybridization, RNA pull-down, RNA immunoprecipitation and immunohistochemical staining showed that circGLIS3 could promoted Ezrin T567 phosphorylation. Further investigation showed that circGLIS3 could be excreted by glioma through exosomes and induced endothelial cells angiogenesis. This study indicates that circGLIS3 is up-regulated in high-grade glioma and contributes to the invasion and angiogenesis of glioma via promoting Ezrin T567 phosphorylation.
Project description:An integrated diagnosis using molecular features is recommended in the updated World Health Organization (WHO) classification. Our aim was to explore the role of MALDI-Mass spectrometry imaging (MSI) coupled to microproteomics in order to classify anaplastic glioma by integration of clinical data.
Project description:Glioma tumors arise from normal glial cells (astrocytes). Gliomas are morphologically and clinically classified into four malignancy grades as Grade I, II, III and IV. Grade I and II comprise low grade gliomas that grow slowly, are well differentiated and have a better prognosis and survival compared to grades III and IV. In contrast, grade III-IV lack endothelial proliferation and are highly vascular with a tendency to infiltrate and have areas of extensive necrosis and hypoxia. In the present study, we used iTRAQ (isobaric tags for relative and absolute quantitation) - based quantitative proteomic approach followed by liquid chromatography and high resolution tandem mass spectrometry (LC-MS/MS) to identify differential membrane and nuclear proteins mapping to Chromosome 12 from three different grades of astrocytoma tumors (WHO Grade II, III and IV) compared to control.
Project description:Diffuse gliomas represent the most prevalent class of primary brain tumor. Despite significant recent advances in the understanding of glioblastoma (WHO IV), its most malignant subtype, lower-grade (WHO II and III) glioma variants remain comparatively understudied, especially in light of their notably variable clinical behavior. To examine the foundations of this heterogeneity, we performed multidimensional molecular profiling, including global transcriptional analysis, on 101 lower-grade diffuse astrocytic gliomas collected at our own institution, and validated our findings using publically available gene expression and copy number data from large independent patient cohorts. We found that IDH mutational status delineated molecularly and clinically distinct glioma subsets, with IDH mutant (IDH mt) tumors exhibiting TP53 mutations, PDGFRA overexpression, and prolonged survival, and IDH wild-type (IDH wt) tumors exhibiting EGFR amplification, PTEN loss, and unfavorable disease outcome. Furthermore, global expression profiling revealed three robust molecular subclasses within lower-grade diffuse astrocytic gliomas, two of which were predominantly IDH mt and one almost entirely IDH wt. IDH mt subclasses were distinguished from each other on the basis of TP53 mutations, DNA copy number abnormalities, and links to distinct stages of neurogenesis in the subventricular zone (SVZ). This latter finding implicates discrete pools of neuroglial progenitors as cells of origin for the different subclasses of IDH mt tumors. In summary, we have elucidated molecularly distinct subclasses of lower-grade diffuse astrocytic glioma that dictate clinical behavior and demonstrate fundamental associations with both IDH mutational status and neuroglial developmental stage. 80 tumor samples, one normal tissue sample (brain)