scholarly journals OTEH-3. Targeted Gene-Expression analysis during malignant transformation in primary and secondary malignant meningioma

2021 ◽  
Vol 3 (Supplement_2) ◽  
pp. ii10-ii11
Author(s):  
Andrea Daniela Maier ◽  
Alessandra Meddis ◽  
Jeppe Haslund-Vinding ◽  
Christian Mirian ◽  
Ausrine Areskeviciute ◽  
...  
Keyword(s):  
Gene Expression ◽  
Malignant Transformation ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Rna Expression ◽  
Malignant Meningioma ◽  
Who Grade ◽  
Significant Difference ◽  
Who Grade Iii ◽  
Grade Iii

Abstract Background Malignant meningiomas comprise 2–5% of all meningiomas. The process of malignant transformation when benign meningiomas (WHO grade I-II) become malignant (WHO grade III) has not previously been investigated in sequential tumour surgeries. Upregulation of FOXM1 expression and DREAM-complex repression have shown phenotypical subgroups correlating with WHO grade and aggressiveness. We investigated the RNA expression of 30 genes central to meningioma biology and 770 genes involved in neuroinflammatory pathways in primary and secondary malignant meningioma patients who underwent one to several operations. Methods We identified a cohort of consecutive malignant meningioma patients treated at Rigshospitalet, Copenhagen from 2000–2020 (n=51) and gathered their malignant tumours and previous WHO grade I/II tumours. The malignant cohort (MC) was counter matched with a benign cohort (BC) where patients had no recurrences during follow-up. RNA expression signatures from 140 samples from the MC and 51 samples from the BC were analysed with the Nanostring Neuroinflammation panel customized with 30 genes known to be relevant in meningioma phenotypes. Results 49% of MC patients had a previous grade I/II meningioma making them secondary malignant meningioma patients. Progression-free survival calculated from first malignant surgery to first recurrence or death showed no significant difference in the primary vs. secondary patients. Preliminary results of single-gene analysis of MC tumours showed FOXM1, MYBL2, TOP2A, BIRC5 expression was higher in WHO grade III samples. Gene-expression signatures in the individual patients and gene ontology enrichment analyses are in process. Conclusions FOXM1, MYBL2, TOP2A, BIRC5 RNA expression levels seem to rise during malignant progression across patients. Gene-expression analysis using the Nanostring technology is feasible and a potentially powerful tool to distinguish meningiomas prone to malignant transformation from truly benign meningiomas.

P04.05 Targeted Gene-Expression analysis during malignant transformation in primary and secondary malignant meningioma

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii19-ii19
Author(s):  
A D Maier ◽  
A Meddis ◽  
J Haslund-Vinding ◽  
C Mirian ◽  
A Areskeviciute ◽  
...  
Keyword(s):  
Gene Expression ◽  
Malignant Transformation ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Rna Expression ◽  
Malignant Meningioma ◽  
Who Grade ◽  
Significant Difference ◽  
Who Grade Iii ◽  
Grade Iii

Abstract BACKGROUND Malignant meningiomas comprise 2–5% of all meningiomas. The process of malignant transformation when benign meningiomas (WHO grade I-II) become malignant (WHO grade III) has not previously been investigated in sequential tumour surgeries. Upregulation of FOXM1 expression and DREAM-complex repression have shown phenotypical subgroups correlating with WHO grade and aggressiveness. We investigated the RNA expression of 30 genes central to meningioma biology and 770 genes involved in neuroinflammatory pathways in primary and secondary malignant meningioma patients who underwent one to several operations. MATERIALS AND METHODS We identified a cohort of consecutive malignant meningioma patients treated at Rigshospitalet, Copenhagen from 2000–2020 (n=51) and gathered their malignant tumours and previous WHO grade I/II tumours. The malignant cohort (MC) was counter matched with a benign cohort (BC) where patients had no recurrences during follow-up. RNA expression signatures from 140 samples from the MC and 51 samples from the BC were analysed with the Nanostring Neuroinflammation panel customized with 30 genes known to be relevant in meningioma phenotypes. RESULTS 49% of MC patients had a previous grade I/II meningioma making them secondary malignant meningioma patients. Progression-free survival calculated from first malignant surgery to first recurrence or death showed no significant difference in the primary vs. secondary patients. Preliminary results of single-gene analysis of MC tumours showed FOXM1, MYBL2, TOP2A, BIRC5 expression was higher in WHO grade III samples. Gene-expression signatures in the individual patients and gene ontology enrichment analyses are in process. CONCLUSIONS FOXM1, MYBL2, TOP2A, BIRC5 RNA expression levels seem to rise during malignant progression across patients. Gene-expression analysis using the Nanostring technology is feasible and a potentially powerful tool to distinguish meningiomas prone to malignant transformation from truly benign meningiomas.

scholarly journals Targeted gene-expression analysis during malignant transformation in primary and secondary malignant meningioma

2021 ◽  
Vol 1 ◽  
pp. 100548
Author(s):  
A.D. Maier ◽  
A. Meddis ◽  
J. Haslund-Vinding ◽  
C. Mirian ◽  
A. Areskeviciute ◽  
...  
Keyword(s):  
Gene Expression ◽  
Malignant Transformation ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Malignant Meningioma ◽  
Targeted Gene Expression

Gene Expression Levels Of Imatinib Transporters and Molecular Response To Imatinib Therapy In Chronic Myeloid Leukemia Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4959-4959
Author(s):  
Hemant Malhotra ◽  
Pratibha Sharma ◽  
Shipra Bhargava ◽  
Bharti Malhotra ◽  
Madhu Kumar
Keyword(s):  
Gene Expression ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Conflicts Of Interest ◽  
Imatinib Therapy ◽  
Molecular Response ◽  
Transcript Expression ◽  
Analysis Study ◽  
Expression Levels ◽  
Significant Difference

Abstract Imatinib mesylate (IM) is the standard first-line treatment for most CML patients. After an initial response, approximately 30 to 40% patients develop resistance to the drug. Various mechanisms of resistance to Imatinib therapy have been identified. One of the mechanisms proposed is varying expression levels of the drug transporters. In the present study, we determined the relative expression levels of Imatinib transporter genes (hOCT1, ABCB1, ABCG2) in CML patients by quantitative real time polymerase chain reaction (qRT-PCR) and correlated these levels with molecular response. One hundred and ten CML patients were considered for gene expression analysis study for hOCT1 gene and eighty seven CML patients were considered for gene expression analysis study for ABCB1 and ABCG2 genes. CML patients who were on IM therapy for more than 2 years were divided into two groups: Responders: patients who achieve a Complete Molecular response (CMR) or a Major Molecular Response (MMR) [bcr/abl: abl ratio <1% as assessed by RQ-PCR] and Non-responders: those without CMR or MMR (bcr/abl: abl ratio =/> 1% as assessed by RQ-PCR). The relative transcript expression levels of the three genes were compared between responders and non-responders. No significant difference in the expression levels of hOCT1, ABCB1 and ABCG2 was found between the two categories - responders versus non-responders (p value > 0.05). The median transcript expression levels of hOCT1, ABCB1 and ABCG2 genes in responders were 30.63, 10.14 and 0.59 versus 40.13, 8.34 and 0.53 in non-responders, respectively. We conclude that, in our study, the mRNA expression levels of IM transporter genes did no correlate with molecular response in CML patients. Disclosures: No relevant conflicts of interest to declare.

2 Intrafollicular injection of asprosin in water buffaloes and the potential role of FBN1 mRNA and asprosin in follicular function

2021 ◽  
Vol 33 (2) ◽  
pp. 108
Author(s):  
E. R. Maylem ◽  
L. Spicer ◽  
E. Atabay ◽  
E. Atabay ◽  
I. Batalha ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Rate ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Mrna Abundance ◽  
Follicular Growth ◽  
Significant Difference ◽  
Follicle Size ◽  
Phosphate Buffered Saline

Fibrillin-1 (FBN1) functions as a structural protein in the ovary, whereas the role of its protein product asprosin remains unknown. Both proteins are encoded by the FBN1 gene; when it is cleaved at the C-terminal end, asprosin is produced. Asprosin acts as an orexigenic hormone and is associated with various metabolic parameters and sex related hormones in women. One goal of this research was to quantify FBN1 and the presumed asprosin receptor, olfactory receptor family 4 subfamily M member 1 (OR4M1) mRNA in water buffalo granulosa cells (GC) and correlate them to aromatase (CYP19A1) gene expression. A second goal was to determine the effect of asprosin on follicular growth invivo. In Experiment 1, ovaries were collected from a local slaughterhouse, GC from small (&lt;6mm) and large (6–13mm) follicles were aspirated, RNA was extracted, and gene expression analysis conducted. In Experiment 2, an intrafollicular injection of asprosin (6μL of asprosin in 194μL of phosphate-buffered saline; to achieve 20ng mL−1) or vehicle (200μL of phosphate-buffered saline; Controls) was given via the ovarian stroma below the dominant follicle of synchronized cows (n=5/group) 1 day after injection of prostaglandin F2α, and follicle sizes were measured daily via transrectal ultrasonography until the day of ovulation. Means were compared using t-test for gene expression analysis, and Pearson correlation coefficients calculated among FBN1, OR4M1, and CYP19A1 gene expression. A repeated-measures ANOVA was used to determine the effect of asprosin on follicle size and growth rate of follicles. In Experiment 1, FBN1 mRNA abundance was 7.51-fold greater in GC of small than large follicles (P&lt;0.05). There was no significant difference in the OR4M1 (57.83±39.89 vs. 38.98±4.86) or CYP19A1 (11.46±3.72 vs. 8.27±4.81) mRNA abundance between the 2 sizes of follicles (P&gt;0.10). Abundance of CYP19A1 mRNA was positively correlated with FBN1 (r=0.55, P&lt;0.05) and OR4M1 mRNA (r=0.50, P&lt;0.05). In Experiment 2, there was a treatment×day interaction (P&lt;0.10) for follicle size and growth rate of follicles. Cows treated with asprosin had a higher growth rate from Day 1 to 2 (1.09±0.39 to 2.37±0.32 mm/day) than placebo cows (1.74±0.55 to 1.05±0.61 mm/day) after injection. Most of the follicles from both treatment groups ovulated 3 days post injection. These findings suggest that FBN1 (and thus asprosin) are present in buffalo GC and may be developmentally expressed. Also, asprosin may induce follicular growth when given invivo. Whether these proteins directly regulate aromatase expression, and therefore oestradiol production, during follicle development will require further study.

Comprehensive genomic analysis in metastatic pancreatic ductal adenocarcinoma (PDAC).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 285-285
Author(s):  
Hui-Li Wong ◽  
Martin Jones ◽  
Peter Eirew ◽  
Joanna Karasinska ◽  
Kasmintan A Schrader ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
De Novo ◽  
Expression Patterns ◽  
Genomic Analysis ◽  
Ductal Adenocarcinoma ◽  
Tumor Biopsy ◽  
Significant Difference ◽  
Gene Expression Signatures

285 Background: In the absence of defined tumor molecular subtypes and validated predictive markers, PDAC has been largely treated as a single disease. Recent studies of molecular subtyping in PDAC reveal a complex mutational landscape with data suggesting the presence of genomic and gene expression signatures that may have prognostic and therapeutic significance. These studies predominantly focused on resected PDAC and lack data on metastatic tumors. We aim to explore the clinical utility of whole genome sequencing (WGS) and transcriptome analysis from metastatic biopsy samples in patients (pts) with advanced PDAC. Methods: Pts with incurable advanced cancers undergo tumor biopsy for in-depth WGS and RNA sequencing (RNASeq) as part of an ongoing prospective study (NCT02155621). Comprehensive bioinformatics analysis is performed to identify somatic cancer aberrations, gene expression changes and cellular pathway abnormalities. Here we describe clinical and molecular data on the subset of pts with advanced PDAC. Results: Sixteen PDAC pts have been enrolled; median age 59 years, 8 males (50%), 10 with de novo metastases (63%). Full WGS and RNASeq were completed in 11 pts (1 failed biopsy, 4 had insufficient tumor). KRAS codon 12 and TP53 mutations were present in all but one pt. CDKN2A and SMAD4 were also frequently altered (7 and 4 pts respectively). Gene expression analysis for classical and basal subtypes similar to those recently described (PMID 26343385) identified 3 and 6 pts with classical and basal expression patterns respectively, and 2 pts with mixed expression. Overall survival (OS) was significantly worse for the basal subtype vs all others (median OS 7 vs. 13.9 months (ms), p = 0.017). When separated into 3 subtypes a significant difference was still noted (median OS 7 ms in basal, 19.2 ms in classical and 11.8 ms in mixed subtype, p = 0.032). Conclusions: WGS analysis demonstrated a similar mutation pattern to that described in resectable PDAC, with no novel actionable mutations identified. Gene expression analysis demonstrated the presence of distinct gene expression signatures significantly associated with outcome, despite small pt numbers. These results need to be validated prospectively in larger cohorts. Clinical trial information: NCT02155621.

scholarly journals Gene Expression Profiling in Human High-Grade Astrocytomas

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Zhongyu Liu ◽  
Zhiqiang Yao ◽  
Chao Li ◽  
Yicheng Lu ◽  
Chunfang Gao
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Anaplastic Astrocytoma ◽  
Low Grade ◽  
Diffuse Astrocytoma ◽  
Who Grade ◽  
Grade Ii ◽  
Who Grade Iii ◽  
Grade Iii

Diffuse astrocytoma of (WHO grade II) has a tendency to progress spontaneously to anaplastic astrocytoma (WHO grade III) and/or glioblastoma (WHO grade IV). However, the molecular basis of astrocytoma progression is still poorly understood. In current study, an essential initial step toward this goal is the establishment of the taxonomy of tumors on the basis of their gene expression profiles. We have used gene expression profiling, unsupervised (hierarchal cluster (HCL) and principal component analysis (PCA)) and supervised (prediction analysis for microarrays (PAM)) learning methods, to demonstrate the presence of three distinct gene expression signatures of astrocytomas (ACMs), which correspond to diffuse or low-grade astrocytoma (WHO grade II), Anaplastic astrocytoma (WHO grade III) and Glioblastoma multiforme (WHO grade IV). We also demonstrate a 171 gene-based classifier that characterize the distinction between these pathologic/molecular subsets of astrocytomas. These results further define molecular subtypes of astrocytomas and may potentially be used to define potential targets and further refine stratification approaches for therapy. In addition, this study demonstrates that combining gene expression analysis with detailed annotated pathway and gene ontology (GO) category resources was applied to highly enriched normal and tumor population; it can yield an understanding of the critical biological mechanism of astrocytomas.

scholarly journals BIOM-43. GLUTAMATE RECEPTOR AND GLUTAMINE METABOLISM PROFILING BY GENE EXPRESSION ANALYSIS AMONG PATIENTS WITH HIGH GRADE GLIOMA (HGG)

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii11-ii11
Author(s):  
Michael Castro ◽  
Nilofar Badra-Azar ◽  
Thomas Kessler ◽  
Moritz Schütte ◽  
Bodo Lange ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hierarchical Clustering ◽  
Glutamate Receptor ◽  
Expression Analysis ◽  
Intracellular Signaling ◽  
Gene Expression Analysis ◽  
Treatment Strategies ◽  
Glutamine Metabolism ◽  
Kainate Receptors ◽  
Grade Iii

Abstract BACKGROUND Glutaminolysis and excessive glutamate production are among the metabolic hallmarks of HGG. In addition to a probable role in causing seizures, autocrine stimulation of metabotropic and ionotropic (NMDA, AMPA, and kainate) receptors are capable of activating intracellular signaling pathways that are tumorigenic and contribute to drug and radiation resistance. While hints of a survival benefit from glutamate receptor targeting have occasionally emerged from the clinic, no single strategy has consistently demonstrated efficacy. Hence, we sought to characterize the magnitude of glutamate receptor overexpression and its diversity across a population of HGG patients. METHODS A set of 41 genes related to glutamate metabolism was selected from the literature. RNA gene counts for TCGA glioblastoma multiforme (N=163) and Grade 3 glioma samples (Astrocytoma=82, Oligodendroglioma=47, Oligoastrocytoma=39) were downloaded from https://portal.gdc.cancer.gov/. Annotation on subtypes and PFS values were obtained from PMID: 24120142 and 26061751. Gene expression normalization as FPKM and hierarchical clustering were performed using R-3.6.0 genes. RESULTS A heatmap with hierarchical clustering for glutamate and glutamine-related genes for the TCGA GBM and grade III glioma samples cohort was generated including colored annotation for the subtype and progression free survival. The graph shows a rough separation into two groups, with grade III gliomas and proneural samples tentatively clustering together and showing higher expression for most of the glutamate related genes. The magnitude of glutaminolysis-related gene over-expression varied significantly across the cohort suggesting a wide variety in the extent of glutamine addiction. CONCLUSION Specific glutamate receptors are commonly upregulated in HGG patients, however the heterogeneity underlying this phenomenon suggests that uniform drug strategies are unlikely to succeed in a diverse population. However, gene expression analysis has utility to identify specific glutamate receptor and glutamine profiles and to inform the treatment strategies for discrete subsets of patients using drugs that are already in the armamentarium.

scholarly journals Multiple Malignant Meningiomas Presenting As Thrombocytopenia

2019 ◽  
Vol 4 (5) ◽  
Keyword(s):  
Mass Effect ◽  
Clinical Development ◽  
Neurological Deficits ◽  
Careful Examination ◽  
Malignant Meningioma ◽  
Dynamic Changes ◽  
Who Grade ◽  
Platelet Production ◽  
Who Grade Iii ◽  
Grade Iii

Backgrounds: Malignant meningiomas are CNS tumors arising from the arachnoids cap cells of the meninges, very rare in infants. Clinically, intracranial hypertension or focal neurological deficits are usually seen for mass effect, rather than leukemoid symptoms. Methods: Retrospectively analyze the detailed clinical development, diagnosis and treatment of a 10-month-old boy initially hospitalized due to leukemoid symptoms. After careful examination, malignant meningioma (WHO grade III) was proved by the biopsy and histopathology. Chemotherapy (three cycle of ifosfamide 100 mg/kg for 3 days, plus doxorubicin 1 mg/ kg for 2 days every 21 days) in combination with imatinib. Results: Dura nodules significantly reduced in size, skin bleeding spots, thrombocytopenia and enlarged superficial lymph almost disappeared. Conclusion: This study was conducted to demonstrate dynamic changes after effective individualized treatment. Meanwhile, we proposed that the invasiveness of meningioma induces somatic DNA damage, leading to abnormal platelet production and megakaryocytic morphology.

scholarly journals Profile of the Nicotinic Cholinergic Receptor Alpha 7 Subunit Gene Expression is Associated with Response to Varenicline Treatment

Genes ◽  
2020 ◽  
Vol 11 (7) ◽  
pp. 746
Author(s):  
Juliana Rocha Santos ◽  
Paulo Roberto Xavier Tomaz ◽  
Jaqueline Ribeiro Scholz ◽  
Patrícia Viviane Gaya ◽  
Tânia Ogawa Abe ◽  
...  
Keyword(s):  
Gene Expression ◽  
Smoking Cessation ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Treatment Success ◽  
Cholinergic Receptor ◽  
Fold Change ◽  
Sample Collection ◽  
Α7 Nachr ◽  
Significant Difference

Introduction: Smoking is considered the leading cause of preventable morbidity and mortality worldwide. Studies have sought to identify predictors of response to smoking cessation treatments. The aim of this study was to analyze a possible association of target gene expression for smoking cessation with varenicline. Methods: We included 74 smokers starting treatment with varenicline. Gene expression analysis was performed through the custom RT² Profiler qPCR array assay, including 17 genes. Times for sample collection were before the start of therapy (T0) and two weeks (T2) and four weeks (T4) after the start of treatment. Results: For gene expression analysis, we selected 14 patients who had success and 13 patients resistant to varenicline treatment. Success was considered to be when a patient achieved tobacco abstinence until the fourth week of treatment and resistant was when a patient had not stopped smoking as of the fourth week of treatment. We observed a significant difference for CHRNA7 gene expression: in the resistant group, samples from T2 and T4 had lower expression compared with T0 (fold change: 0.38, P = 0.007; fold change: 0.67, P = 0.004; respectively). Conclusion: This exploratory clinical study, searching for a possible predictor of effectiveness for varenicline, reaffirmed the association of the α7 nAChR subunit for nicotine dependence and smoking therapy effectiveness with varenicline.

scholarly journals SLAMF6 is associated with the susceptibility and severity of rheumatoid arthritis in the Chinese population

2022 ◽  
Vol 17 (1) ◽  
Author(s):  
Guodong Xia ◽  
Yetian Li ◽  
Wei Pan ◽  
Chengmei Qian ◽  
Lin Ma ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Expression Analysis ◽  
Chinese Population ◽  
Gene Expression Analysis ◽  
Genome Wide Association Study ◽  
Tissue Expression ◽  
Chi Square ◽  
Significant Difference ◽  
Student’S T

Abstract Objectives A recently published genome-wide association study identified six novel loci associated with rheumatoid arthritis (RA) in Korean population. We aimed to investigate whether these newly reported RA-risk loci are associated with RA in the Chinese population and to further characterize the functional role of the susceptible gene. Methods The susceptible variants of RA were genotyped in 600 RA patients and 800 healthy controls, including rs148363003 of SLAMF6, rs117605225 of CXCL13, rs360136 of SWAP70, rs111597524 of NFKBIA, rs194757 of ZFP36L1 and rs1547233 of LINC00158. Synovial tissues were collected from the knee joint of 50 RA patients and 40 controls without osteoarthritis for the gene expression analysis. Inter-group comparisons were performed with the Chi-square test for genotyping data or with Student's t-test for gene expression analysis. Result For rs148363003 of SLAMF6, RA patients were observed to have a significantly lower frequency of genotype CC (4.5% vs. 0.9%, p = 0.004) as compared with the controls. The frequency of allele C was remarkably higher in the patients than in the controls (11.5% vs. 8.0%, p = 0.002), with an odds ratio of 1.49 (95% CI = 1.16–1.92). There was no significant difference between the patients and the controls regarding genotype or allele frequency of the other 5 variants. The mRNA expression of SLAMF6 was 1.6 folds higher in the RA patients than in the controls. Moreover, SLAMF6 expression was 1.5 folds higher in patients with genotype CC than in the patients with genotype TT. Conclusions SLAMF6 was associated with both the susceptibility and severity of RA in the Chinese population. Moreover, rs148363003 could be a functional variant regulating the tissue expression of SLAMF6 in RA patients. It is advisable to conduct further functional analysis for a comprehensive knowledge on the contribution of this variant to the development of RA.

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