scholarly journals GENE-20. IDENTIFYING POTENTIAL GENES AND MECHANISMS DRIVING IDH-MUTANT GLIOMA PROGRESSION AND RECURRENCE THROUGH RNA-SEQUENCING

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi101-vi102
Author(s):  
Angela Cho ◽  
Amanda Hudson ◽  
Emily Colvin ◽  
Sarah Hayes ◽  
Helen Wheeler ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Treatment Resistance ◽  
Differentially Expressed ◽  
Low Grade ◽  
Sequencing Platform ◽  
Radiotherapy Group ◽  
Treatment Naïve ◽  
Radiotherapy Alone ◽  
Longitudinal Comparison ◽  
Glioma Progression

Abstract Gliomas are the most common primary brain tumors in adults. IDH-mutated low-grade gliomas of astrocytic lineage (astrocytomas) have a relatively indolent clinical course; however, over time they progress to a higher grade. Molecular studies revealed recurrent tumors harbor more mutations upon malignant progression when treated with chemotherapy and/or radiotherapy compared to treatment-naïve tumors. However, genes which promote progression and recurrence in these tumors are unknown. This study aims to identify the transcriptional drivers of progression and recurrence of IDH-mutant gliomas. Longitudinal comparison of transcriptional profiles was performed on 6 matched pairs of primary lesions and their higher-grade recurrent lesion collected 1 to 8 years later. Three patients received no treatment and three patients received radiotherapy alone between their first and second surgeries. RNA was extracted from frozen specimens and following quality control, analyzed with the Illumina Next-Generation Sequencing platform (HiSeq HT paired end, TruSeq Kit). Comparison of RNA-seq results from primary and recurrent specimens identified 2042 differentially expressed genes (FC ≥2) for the no-treatment group and 2066 differentially expressed genes for the radiotherapy group. These genes include CADM2, SPP1, NDRG2 and CA9 which are associated with pro-tumor processes such as signal transduction, cell adhesion and treatment resistance. Validation is in progress. Identifying key genes driving glioma progression and recurrence will increase our understanding of the nature of these tumors and reveal core processes and potential novel targets that may be exploited for additional therapies for this deadly cancer.

scholarly journals Toxoplasma infection alters dopamine-sensitive behaviors and host gene expression patterns associated with neuropsychiatric disease

2021 ◽  
Author(s):  
Graham L. Cromar ◽  
Jonathan Epp ◽  
Ana Popovic ◽  
Yusing Gu ◽  
Violet Ha ◽  
...  
Keyword(s):  
Gene Expression ◽  
Differentially Expressed Genes ◽  
Expression Patterns ◽  
Neurocognitive Disorders ◽  
Differentially Expressed ◽  
Gene Expression Patterns ◽  
Low Grade ◽  
Cocaine Exposure ◽  
Multiple Testing Correction ◽  
The Impact

ABSTRACTToxoplasma gondii is a single celled parasite thought to infect 1 in 3 worldwide. During chronic infection, T. gondii can migrate to the brain where it promotes low-grade neuroinflammation with the capacity to induce changes in brain morphology and behavior. Consequently, infection with T. gondii has been linked with a number of neurocognitive disorders including schizophrenia (SZ), dementia, and Parkinson’s disease. Beyond neuroinflammation, infection with T. gondii can modulate the production of neurotransmitters, such as dopamine. To further dissect these pathways and examine the impact of altered dopaminergic sensitivity in T. gondii-infected mice on both behavior and gene expression, we developed a novel mouse model, based on stimulant-induced (cocaine) hyperactivity. Employing this model, we found that infection with T. gondii did not alter fear behavior but did impact motor activity and neuropsychiatric-related behaviurs. While both behaviors may help reduce predator avoidance, consistent with previous studies, the latter finding is reminiscent of neurocognitive disorders. Applying RNASeq to two relevant brain regions, striatum and hippocampus, we identified a broad upregulation of immune responses. However, we also noted significant associations with more meaningful neurologically relevant terms were masked due to the sheer number of terms incorporated in multiple testing correction. We therefore performed a more focused analysis using a curated set of neurologically relevant terms revealing significant associations across multiple pathways. We also found that T. gondii and cocaine treatments impacted the expression of similar functional pathways in the hippocampus and striatum although, as indicated by the low overlap among differentially expressed genes, largely via different proteins. Furthermore, while most differentially expressed genes reacted to a single condition and were mostly upregulated, we identified gene expression patterns indicating unexpected interactions between T. gondii infection and cocaine exposure. These include sets of genes which responded to cocaine exposure but not upon cocaine exposure in the context of T. gondii infection, suggestive of a neuroprotective effect advantageous to parasite persistence. Given its ability to uncover such complex relationships, we propose this novel model offers a new perspective to dissect the molecular pathways by which T. gondii infection contributes to neuropsychiatric disorders such as schizophrenia.

Integrated Transcriptomic Analysis of Necrosis-related Gene in Diffuse Gliomas

2019 ◽  
Vol 80 (04) ◽  
pp. 240-249
Author(s):  
Jiajia Wang ◽  
Jie Ma
Keyword(s):  
Gene Expression ◽  
High Risk ◽  
Differentially Expressed Genes ◽  
Expression Profiles ◽  
Prognostic Index ◽  
Gene Expression Profiles ◽  
Risk Groups ◽  
Low Risk ◽  
Differentially Expressed ◽  
Low Grade

Glioblastoma multiforme (GBM), an aggressive brain tumor, is characterized histologically by the presence of a necrotic center surrounded by so-called pseudopalisading cells. Pseudopalisading necrosis has long been used as a prognostic feature. However, the underlying molecular mechanism regulating the progression of GBMs remains unclear. We hypothesized that the gene expression profiles of individual cancers, specifically necrosis-related genes, would provide objective information that would allow for the creation of a prognostic index. Gene expression profiles of necrotic and nonnecrotic areas were obtained from the Ivy Glioblastoma Atlas Project (IVY GAP) database to explore the differentially expressed genes.A robust signature of seven genes was identified as a predictor for glioblastoma and low-grade glioma (GBM/LGG) in patients from The Cancer Genome Atlas (TCGA) cohort. This set of genes was able to stratify GBM/LGG and GBM patients into high-risk and low-risk groups in the training set as well as the validation set. The TCGA, Repository for Molecular Brain Neoplasia Data (Rembrandt), and GSE16011 databases were then used to validate the expression level of these seven genes in GBMs and LGGs. Finally, the differentially expressed genes (DEGs) in the high-risk and low-risk groups were subjected to gene ontology enrichment, Kyoto Encyclopedia of Genes and Genomes pathway, and gene set enrichment analyses, and they revealed that these DEGs were associated with immune and inflammatory responses. In conclusion, our study identified a novel seven-gene signature that may guide the prognostic prediction and development of therapeutic applications.

scholarly journals Ileal transcriptomic analysis in paediatric Crohn’s disease reveals IL17- and NOD-signalling expression signatures in treatment-naïve patients and identifies epithelial cells driving differentially expressed genes

2020 ◽  
Author(s):  
James J Ashton ◽  
Konstantinos Boukas ◽  
James Davies ◽  
Imogen S Stafford ◽  
Andres F Vallejo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Single Cell ◽  
Differentially Expressed Genes ◽  
Gene Signature ◽  
Oncostatin M ◽  
Differentially Expressed ◽  
Single Cell Sequencing ◽  
Treatment Naïve ◽  
Ileal Tissue

Abstract Background/Aims Crohn’s disease (CD) arises through host-environment interaction. Abnormal gene expression results from disturbed pathway activation or response to bacteria. We aimed to determine activated pathways and driving cell types in paediatric CD. Methods - We employed contemporary targeted autoimmune RNA sequencing, in parallel to single-cell sequencing, to ileal tissue derived from paediatric CD and controls. Weighted-gene-co-expression-network-analysis (WGCNA) was performed and differentially expressed genes (DEGs) were determined. We integrated clinical data to determine co-expression modules associated with outcomes. Results - Twenty-seven treatment-naive CD (TN-CD), 26 established-CD patients and 17 controls were included. WGCNA revealed a 31-gene signature characterising TN-CD patients, but not established-CD, or controls. The CSF3R gene is a hub within this module and is key in neutrophil expansion and differentiation. Antimicrobial genes including S100A12 and the calprotectin subunit S100A9 were significantly upregulated in TN CD compared to controls (p=2.61x10 -15 and p=9.13x10 -14, respectively) and established-CD (both p=0.0055). Gene-enrichment analysis confirmed upregulation of the IL17-, NOD- and Oncostatin-M-signalling pathways in TN-CD patients, identified in both WGCNA and DEG analyses. An upregulated gene-signature was enriched for transcripts promoting Th17-cell differentiation and correlated with prolonged time to relapse (correlation-coefficient-0.36, p=0.07).Single-cell sequencing of TN-CD patients identified specialised epithelial cells driving differential expression of S100A9. Cell groups, determined by single-cell gene-expression, demonstrated enrichment of IL17-signalling in monocytes and epithelial cells. Conclusion - Ileal tissue from treatment naïve paediatric patients is significantly upregulated for genes driving IL17-, NOD- and Oncostatin-M-signalling. This signal is driven by a distinct subset of epithelial cells expressing antimicrobial gene transcripts.

scholarly journals Transcriptional Networks Identify BRPF1 as a Potential Drug Target Based on Inflammatory Signature in Primary Lower-Grade Gliomas

2021 ◽  
Vol 11 ◽  
Author(s):  
Mingyang Xia ◽  
Huiyao Chen ◽  
Tong Chen ◽  
Ping Xue ◽  
Xinran Dong ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Drug Target ◽  
Drug Targets ◽  
Differentially Expressed ◽  
Transcriptional Networks ◽  
Low Grade ◽  
Normal Brain ◽  
Lower Grade ◽  
Potential Drug Target ◽  
Potential Drug

Gliomas are the most common tumors of the central nervous system and are classified into grades I-IV based on their histological characteristics. Lower-grade gliomas (LGG) can be divided into grade II diffuse low-grade gliomas and grade III moderate gliomas and have a relatively good prognosis. However, LGG often develops into high-grade glioma within a few years. This study aimed to construct and identify the prognostic value of an inflammatory signature and discover potential drug targets for primary LGG. We first screened differentially expressed genes in primary LGG (TCGA) compared with normal brain tissue (GTEx) that overlapped with inflammation-related genes from MSigDB. After survival analysis, nine genes were selected to construct an inflammatory signature. LGG patients with a high inflammatory signature score had a poor prognosis, and the inflammatory signature was a strong independent prognostic factor in both the training cohort (TCGA) and validation cohort (CGGA). Compared with the low-inflammatory signature group, differentially expressed genes in the high-inflammatory signature group were mainly enriched in immune-related signaling pathways, which is consistent with the distribution of immune cells in the high- and low-inflammatory signature groups. Integrating driver genes, upregulated genes and drug targets data, bromodomain and PHD finger-containing protein 1 (BRPF1) was selected as a potential drug target. Inhibition of BRPF1 function or knockdown of BRPF1 expression attenuated glioma cell proliferation and colony formation.

scholarly journals De Novo Assembly and Transcriptome Profiling of Ethiopian Lowland Bamboo Oxytenanthera Abyssinica (A. rich) Munro Under Drought and Salt Stresses

2019 ◽  
Vol 13 (1) ◽  
pp. 6-17
Author(s):  
Muhamed Adem ◽  
Dereje Beyene ◽  
Tileye Feyissa ◽  
Kai Zhao ◽  
Tingbo Jiang
Keyword(s):  
Differentially Expressed Genes ◽  
De Novo ◽  
Transcriptome Profiling ◽  
Global Gene Expression ◽  
Perennial Grasses ◽  
Differentially Expressed ◽  
Cdna Libraries ◽  
Protein Families ◽  
Sequencing Platform ◽  
Genome Wide

Background: Bamboos are perennial grasses classified under family Poaceae and subfamily Bambusoideae and are among the fastest growing plants on earth. Despite ecological and economic significances, Ethiopian lowland bamboo (O. abyssinica) lacks global gene expression under abiotic stress. Methods: Plastic pot germinated seedlings of O. abyssinica were subjected to 200 µm NaCl and 25% PEG-6000 (Poly Ethylene glycol) to induce salt and drought stress, respectively. Using the Illumina sequencing platform, fifteen cDNA libraries were constructed and sequenced to generate the first drought and salt stress transcriptome profiling of the species so as to elucidate genome-wide transcriptome changes in response to such stresses. Results: Following quality control, 754,444,646 clean paired-ends reads were generated, and then de novo assembled into 406,181 unigenes. Functional annotation against the public databases presented annotation of 217,067 (53.4%) unigenes, where NCBI-Nr 203,777, Swissport 115,741, COG 81,632 and KEGG 80,587. Prediction of Transcripts Factors (TFs) have generated 4,332 TFs organized into 64 TF families. Analysis of Differentially Expressed Genes (DEGs) provided 65,471 genes where 569 genes belong to all stresses. Protein families with a higher number of differentially expressed genes include bZIP (49), WRKY (43), MYB (38), AP2/ERF (30), HD-ZIP (25) and MYB related (21). Conclusion: In addition to revealing the genome-wide level appraisal of transcriptome resources of the species, this study also uncovered the comprehensive understanding of key stress responsive protein-coding genes, protein families and pathways which could be used as the basis for further studies.

GENE EXPRESSION ANALYSIS OF A DEDIFFERENTIATED LIPOSARCOMA — DIFFERENCES BETWEEN HIGH AND LOW GRADE AREAS: ANALYSIS OF TWO CASES AND LITERATURE REVIEW

2005 ◽  
Vol 09 (01) ◽  
pp. 9-20 ◽  
Author(s):  
Meera R. Hameed ◽  
Tao-Zhen Lin ◽  
Frederick Coffman ◽  
Marion C. Cohen ◽  
Helen Fernandes ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Expression Patterns ◽  
Soft Tissue Sarcomas ◽  
Differentially Expressed ◽  
Dedifferentiated Liposarcoma ◽  
Biological Behavior ◽  
Low Grade ◽  
High Grade ◽  
High Grade Sarcoma ◽  
Well Differentiated

The phenomenon of dedifferentiation typically occurs in soft tissue sarcomas where a low grade or well-differentiated tumor shows an abrupt transformation to a high-grade sarcoma without lineage specificity. The biological behavior and metastatic potential of these tumors is dictated by the dedifferentiated phenotype. Tumor material was available from two dedifferentiated liposarcomas. We performed cDNA microarray analysis of a dedifferentiated liposarcoma in which the atypical lipomatous/well-differentiated and dedifferentiated portions were grossly distinct, to find differentially expressed genes in the dedifferentiated component compared to the well-differentiated component. There were 100 differentially expressed genes, both up- and down-regulated in the high grade sarcoma. In addition, we performed RT-PCR on selected genes in both cases to confirm the microarray findings. We discuss the expression patterns of these genes in comparison to other studies in the literature.

scholarly journals ELTD1-deletion reduces vascular abnormality and improves T-cell recruitment after PD-1 blockade in glioma

2021 ◽  
Author(s):  
Hua Huang ◽  
Maria Georganaki ◽  
Lei Liu Conze ◽  
Bàrbara Laviña ◽  
Luuk van Hooren ◽  
...  
Keyword(s):  
T Cell ◽  
Inflammatory Response ◽  
Differentially Expressed Genes ◽  
Vascular Function ◽  
Patient Survival ◽  
Vascular Dysfunction ◽  
Treatment Resistance ◽  
Differentially Expressed ◽  
Vascular Abnormality

Abstract Background Tumor vessels in glioma are molecularly and functionally abnormal, contributing to treatment resistance. Proteins differentially expressed in glioma vessels can change vessel phenotype and be targeted for therapy. ELTD1 (Adgrl4) is an orphan member of the adhesion G-protein-coupled receptor family upregulated in glioma vessels, and has been suggested as a potential therapeutic target. However, the role of ELTD1 in regulating vessel function in glioblastoma is poorly understood. Methods ELTD1 expression in human gliomas and its association with patient survival was determined using tissue microarrays and public databases. The role of ELTD1 in regulating tumor vessel phenotype was analyzed using orthotopic glioma models and ELTD1 -/- mice. Endothelial cells isolated from murine gliomas were transcriptionally profiled to determine differentially expressed genes and pathways. The consequence of ELTD1-deletion on glioma immunity was determined by treating tumor bearing mice with PD-1-blocking antibodies. Results ELTD1 levels were upregulated in human glioma vessels, increased with tumor malignancy, and were associated with poor patient survival. Progression of orthotopic gliomas was not affected by ELTD1-deletion, however, tumor vascular function was improved in ELTD1 -/- mice. Bioinformatic analysis of differentially expressed genes indicated increased inflammatory response and decreased proliferation in tumor endothelium in ELTD1 -/- mice. Consistent with an enhanced inflammatory response, ELTD1-deletion improved T-cell infiltration in GL261-bearing mice after PD-1 checkpoint blockade. Conclusion Our data demonstrate that ELTD1 participates in inducing vascular dysfunction in glioma, and suggests that targeting of ELTD1 may normalize the vessels and improve the response to immunotherapy.

scholarly journals Comparison of Approaches to Transcriptomic Analysis in Multi-Sampled Tumors

2021 ◽  
Author(s):  
Anson T. Ku ◽  
Scott Wilkinson ◽  
Adam G. Sowalsky
Keyword(s):  
Differentially Expressed Genes ◽  
Repeated Measures ◽  
Statistical Power ◽  
Linear Models ◽  
Expression Profiles ◽  
Differentially Expressed Gene ◽  
Gene Expression Profiles ◽  
Treatment Resistance ◽  
Ground Truth ◽  
Differentially Expressed

Intratumoral heterogeneity is a well-documented feature of human cancers associated with outcome and treatment resistance. However, a heterogeneous tumor transcriptome contributes an unknown level of variability to analyses of differentially expressed genes that may contribute to phenotypes of interest, including treatment response. Although current clinical practice and the vast majority of research studies use a single sample from each patient, decreasing costs in sequencing technologies and computing costs have made repeated-measures analyses increasingly economical. Repeatedly sampling the same tumor increases the statistical power of differentially expressed gene analysis that is indispensable towards downstream analysis and also increases ones understanding of within-tumor variance that may affect conclusions. Here, we compared five different methods for analyzing gene expression profiles derived from repeated sampling of human prostate tumors in two separate cohorts of patients. We also benchmarked the sensitivity of generalized linear models to linear mixed models for identifying differentially expressed genes contributing to relevant prostate cancer pathways based on a ground truth model.

Sign in / Sign up

Export Citation Format

Share Document