Project description:Astrocytoma is a common type of glioma and a frequent cause of brain tumour-related epilepsy. Although the link between glioma and epilepsy is well established, the precise mechanisms underlying epileptogenesis in astrocytoma remain poorly understood. In this study, we performed proteomic analysis of astrocytoma tissue from patients with and without seizures using mass spectrometry-based techniques. We detected 131 differentially expressed proteins (42 upregulated and 89 downregulated). Proteins upregulated in patients with seizures were mostly related to an increase in energy metabolism. Moreover, glial fibrillary acidic protein, which is involved in maintaining normal axonal structures, was abnormally highly expressed in patients with seizures. Proteins downregulated in patients with seizures included those involved in trans-synaptic signalling and gamma-aminobutyric acid synaptic transmission. Interestingly, comparison of protein expression profiles from our cohort with those from a previous study of patients with epilepsy due to other causes showed that the collapsin response mediator protein family of axonal growth regulators was highly expressed only in patients with seizures due to astrocytomas. Further studies of the proteins identified here are required to determine their potential as biomarkers and therapeutic targets.
Project description:Objectives: Epileptogenesis in human glioma is linked to increased glutamate signaling that is primarily facilitated by xCT, suggesting it as a pharmacological target for anti-seizure medication (ASM). Here, we investigated the expression of xCT in glioma-associated epilepsy and investigated the impact of both tumor-associated epilepsy and xCT expression levels on the glioma proteome. Methods: We quantified the expression of xCT and its subunit SLC3A2 by immunoblot in snap-frozen tissue of tumor treatment-naïve IDH-mutant and IDH-wildtype gliomas (n=93) in cases with and without epilepsy (controls)and control cases and compared it to the levels of excitatory amino acid transporter 2 (EAAT2) and the solute carrier family 1 member 4 (SLC1A4). Additionally, we performed whole cell proteomics in IDH-wildtype glioblastoma (GB) from 16 patients with or without epilepsy, and with low or high xCT protein expression. Results: In cases with epilepsy, we observed a trend towards higher expression of xCT and found that EAAT2 and SLC1A4 were significantly higher expressed. Quantitative proteomics of IDH-wildtype GB with epilepsy versus control identified 214 proteins to be significantly regulated. Upregulated proteins showed enrichment for Gene Ontology (GO) terms involving neurotransmitter and amino acid turnover as well as lipid metabolism. Within the epilepsy group, we found a distinction between xCT low- and high-expressing tumors. Of the 231 proteins that were increased in xCT high-expressing tumors, 35 overlapped with proteins upregulated in the epilepsy cohort. These proteins again clustered for GO-BP terms involving neurotransmitter and amino acid metabolism. In addition, xCT high-expressing tumors showed upregulation of proteins that clustered for myelination and regulation of synaptic plasticity. In the survival analysis, epilepsy and high xCT expression did not influence the outcome of patients with either IDH-mutant or IDH-wildtype tumors. Significance: Our results show differences in the proteome of gliomas with and without epilepsyseizures and illustrate that xCT expression levels impact the protein network of these tumors. Our study provides insights into the biological network of these tumors that may be relevant for the development of targeted ASM.
Project description:To investigate the potential pathogenic mechanism of glioma-related epilepsy (GRE), we have employed analyzing of the dynamic expression profiles of microRNA/ mRNA/ lncRNA in brain tissues of glioma patients. Brain tissues of 16 patients with GRE and nine patients with glioma without epilepsy (GNE) were collected. The total RNA was dephosphorylated, labeled, and hybridized to the Agilent Human miRNA Microarray, Release 19.0, 8x60K. The cDNA was labeled and hybridized to the Agilent LncRNA+mRNA Human Gene Expression Microarray V3.0, 4x180K. The raw data was extracted from hybridized images using Agilent Feature Extraction, and quantile normalization was performed using the Agilent GeneSpring. We found that three differentially expressed miRNAs (miR-10a-5p, miR-10b-5p, miR-629-3p), six differentially expressed lncRNAs (TTN-AS1, LINC00641, SNHG14, LINC00894, SNHG1, OIP5-AS1), and 49 differentially expressed mRNAs may play a vitally critical role in developing GRE.
Project description:Tumefactive demyelinating lesion (TDL) is an immune-mediated disease which could appear like glioma. Here, we perform integrative and comparative single-cell RNA sequencing (ScRNA-seq) transcriptomic analysis on TDL and glioma lesions.
Project description:Primary outcome(s): 1. Evaluation of genome abnormality and gene expression by omics analysis of tumor etc. 2. TCR repertoire analysis and RNA expression analysis etc. of T cells in tumor tissue and peripheral blood. 3. Prediction and identification of tumor neo-antigen and evaluation of immunogenicity etc. 4. Analyze ctDNA(16S rRNA PCR) and feces of patients with advanced solid malignancies over time to profile and monitor cancer-related genomic alterations 5. Assessment of the relationship between the analysis above and clinical pathological features or therapeutic efficacy etc.
Project description:MicroRNAs (miRNAs) have been found to participate in the pathogenesis of several neurological diseases including epilepsy. To date, the expression and functions of miRNAs in chronic temporal lobe epilepsy (TLE), the most common type of refractory epilepsy in adults, have not been well characterized. Here, we adopted high-throughput sequencing to investigate miRNA expression profile in a chronic TLE model induced by amygdala stimulation
Project description:To examine fosB regulation of neurogenesis, depression and epilepsy, we compared the gene expression profiles of wild type, fosBd/d and fosB-null mice by microarray analysis. Microarray analysis revealed that genes related to neurogenesis, depression and epilepsy are altered in the hippocampus of fosB-null mice.