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.
2022-06-07 | GSE199759 | GEO
Project description:Integrative analysis of expression profile in the glioma-related epilepsy
Project description:BackgroundSeizures are a common symptom in glioma patients, and they can cause brain dysfunction. However, the mechanism by which glioma-related epilepsy (GRE) causes alterations in brain networks remains elusive.ObjectiveTo investigate the potential pathogenic mechanism of GRE by analyzing the dynamic expression profiles of microRNA/ mRNA/ lncRNA in brain tissues of glioma patients.MethodsBrain tissues of 16 patients with GRE and 9 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, 8 × 60 K. The cDNA was labeled and hybridized to the Agilent LncRNA + mRNA Human Gene Expression Microarray V3.0, 4 × 180 K. The raw data was extracted from hybridized images using Agilent Feature Extraction, and quantile normalization was performed using the Agilent GeneSpring. P-value < 0.05 and absolute fold change > 2 were considered the threshold of differential expression data. Data analyses were performed using R and Bioconductor.ResultsWe found that 3 differentially expressed miRNAs (miR-10a-5p, miR-10b-5p, miR-629-3p), 6 differentially expressed lncRNAs (TTN-AS1, LINC00641, SNHG14, LINC00894, SNHG1, OIP5-AS1), and 49 differentially expressed mRNAs play a vitally critical role in developing GRE. The expression of GABARAPL1, GRAMD1B, and IQSEC3 were validated more than twofold higher in the GRE group than in the GNE group in the validation cohort. Pathways including ECM receptor interaction and long-term potentiation (LTP) may contribute to the disease's progression. Meanwhile, We built a lncRNA-microRNA-Gene regulatory network with structural and functional significance.ConclusionThese findings can offer a fresh perspective on GRE-induced brain network changes.
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: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:Label-free Proteomic profile of the dentate gyrus (dorsal and ventral) and CA3 (dorsal and ventral) microdissected from the hippocampus of the pilocarpine model of Mesial Temporal Lobe Epilepsy.
Project description:Mesial temporal lobe epilepsy (mTLE) is a chronic neurological disease characterized by recurrent seizures. The pathogenic mechanisms underlying TLE involve defects in post-transcriptional regulation of gene expression. So far, transcriptome profiles from epileptic tissue have been performed using whole cells, thereby lacking information on RNA localization and function at a subcellular level. In this project, we set out to understand the compartment-specific total RNA profile of human mTLE tissue samples. For this, we had established a protocol to isolate cytoplasmic and nuclear compartments from human hippocampal tissue. Subcellular RNA was isolated from resected hippocampal (HC) and neo-cortical (Cx) tissue from mTLE no hippocampal sclerosis (non-HS) and mTLE HS International League Against Epilepsy (ILAE) Type 1 or mTLE+HS patients and postmortem control tissue. Later, we used total RNA sequencing (RNA-seq) to profile for the distinct RNA localization in mTLE in comparison to postmortem control tissue and identified disease related pathways in individual cell compartments. Here we report the total RNAseq (coding and non-coding) data.
Project description:This study describes the survival outcomes of advanced stage breast, colorectal, ovarian and pancreatic cancer patients receiving advanced integrative oncology (AIO) treatment at participating North American integrative oncology clinics. This study also aims to describe the integrative treatments recommended by naturopathic doctors (NDs) for these participants alongside their conventional care treatments. Sub-studies will evaluate health-related quality of life, cost of cancer care, and qualitative experience of care in a subset of Canadian participants.