scholarly journals The utility of plasma circulating cell-free messenger RNA as a biomarker of glioma: a pilot study

2021 ◽  
Author(s):  
Michael Itak Ita ◽  
Jiang Huai Wang ◽  
André Toulouse ◽  
Chris Lim ◽  
Noel Fanning ◽  
...  
Keyword(s):  
Messenger Rna ◽  
High Grade Glioma ◽  
Low Grade Glioma ◽  
Fold Change ◽  
Tumour Resection ◽  
Low Grade ◽  
High Grade ◽  
Significant Differential Expression ◽  
Positive Correlation ◽  
Transcriptomic Profile

Abstract Background Research into the potential utility of plasma-derived circulating cell-free nucleic acids as non-invasive adjuncts to radiological imaging have been occasioned by the invasive nature of brain tumour biopsy. The objective of this study was to determine whether significant differences exist in the plasma transcriptomic profile of glioma patients relative to differences in their tumour characteristics, and also whether any observed differences were representative of synchronously obtained glioma samples and TCGA glioma-derived RNA. Methods Blood samples were collected from twenty glioma patients prior to tumour resection. Plasma ccfmRNAs and glioma-derived RNA were extracted and profiled. Results BCL2L1, GZMB, HLA-A, IRF1, MYD88, TLR2, and TP53 genes were significantly over-expressed in glioma patients (p < 0.001, versus control). GZMB and HLA-A genes were significantly over-expressed in high-grade glioma patients (p < 0.001, versus low-grade glioma patients). Moreover, the fold change of the BCL2L1 gene was observed to be higher in patients with high-grade glioma (p = 0.022, versus low-grade glioma patients). There was positive correlation between the magnitude of fold change of differentially expressed genes in plasma- and glioma-derived RNA (Spearman r = 0.6344, n = 14, p = 0.017), and with the mean FPKM in TCGA glioma-derived RNA samples (Spearman r = 0.4614, n = 19, p < 0.05). There was positive correlation between glioma radiographic tumour burden and the magnitude of fold change of the CSF3 gene (r = 0.9813, n = 20, p < 0.001). Conclusion We identified significant differential expression of genes involved in cancer inflammation and immunity crosstalk among patients with different glioma grades, and there was positive correlation between their transcriptomic profile in plasma and tumour samples, and with TCGA glioma-derived RNA.

O51 The utility of plasma circulating cell-free messenger RNA as a biomarker of glioma: a pilot study

2021 ◽  
Vol 108 (Supplement_5) ◽  
Author(s):  
M I Ita ◽  
J H Wang ◽  
A Toulouse ◽  
C H Lim ◽  
N Fanning ◽  
...  
Keyword(s):  
Messenger Rna ◽  
High Grade Glioma ◽  
Fold Change ◽  
Tumour Resection ◽  
Low Grade ◽  
Messenger Rnas ◽  
Significant Differential Expression ◽  
Positive Correlation ◽  
Transcriptomic Profile ◽  
Tumour Biopsy

Abstract Introduction Research into the potential utility of plasma-derived circulating cell-free nucleic acids as non-invasive adjuncts to radiological imaging has been occasioned by the invasive nature of brain tumour biopsy. Circulating-cell-free messenger RNAs are short fragments of RNA present in blood. The objective of this study was to determine whether significant differences exist in the plasma transcriptomic profile of glioma patients relative to differences in their tumour characteristics, and also whether any observed differences were representative of synchronously obtained glioma samples and TCGA glioma derived RNA. Method Blood samples were collected from twenty-nine patients prior to tumour resection. Plasma ccfmRNA and glioma derived RNA were extracted and profiled. Result BCL2L1, CXCL5, GZMB, HLA-A, HLA-C, IRF1, MYD88, TGFB1, TLR2, and TP53 genes were significantly over-expressed in glioma (high-grade-glioma-HGG and low-grade-glioma-LGG) patients (P &lt; 0.05, versus control). BCL2L1, GZMB and HLA-A genes were significantly over-expressed in HGG patients (P &lt; 0.05, versus LGG patients). There was positive correlation between the magnitude of fold change of differentially expressed genes in plasma and glioma derived RNA (Spearman r = 0.6344, n = 14, P = 0.017), and with the mean FPKM of TCGA glioma derived RNA samples (Spearman r = 0.4614, n = 19, P = 0.047). There was positive correlation between glioma radiographic tumour burden and the magnitude of fold change of CSF3 gene (r = 0.9813, n = 20, P &lt; 0.001). Conclusion We identified significant differential expression of genes involved in cancer inflammation and immunity among patients with different glioma grades, and we identified positive correlation between the plasma transcriptomic profile and tumour samples, and with TCGA glioma derived RNA. Take-home Message The plasma transcriptomic profile of glioma patients appears to be representative of synchronously obtained glioma samples.

scholarly journals 1095 The Utility of Plasma Circulating Cell-Free Messenger RNA as A Biomarker of Glioma: A Pilot Study

2021 ◽  
Vol 108 (Supplement_6) ◽  
Author(s):  
M Ita ◽  
J H Wang ◽  
A Toulouse ◽  
C Lim ◽  
N Fanning ◽  
...  
Keyword(s):  
Messenger Rna ◽  
High Grade Glioma ◽  
Fold Change ◽  
Tumour Resection ◽  
Low Grade ◽  
Messenger Rnas ◽  
Significant Differential Expression ◽  
Positive Correlation ◽  
Transcriptomic Profile ◽  
Tumour Biopsy

Abstract Introduction Research into the potential utility of plasma-derived circulating-cell-free nucleic acids as non-invasive adjuncts to radiological imaging has been occasioned by the invasive nature of brain tumour biopsy. Circulating-cell-free messenger RNAs are short fragments of RNA present in blood. The objective of this study was to determine whether significant differences exist in the plasma transcriptomic profile of glioma patients relative to differences in their tumour characteristics, and also whether any observed differences were representative of synchronously obtained glioma samples and TCGA glioma derived RNA. Method Blood samples were collected from twenty-nine patients prior to tumour resection. Plasma-ccfmRNA and glioma derived RNA were extracted and profiled. Results BCL2L1, CXCL5, GZMB, HLA-A, HLA-C, IRF1, MYD88, TGFB1, TLR2, and TP53 genes were significantly over-expressed in glioma (high-grade-glioma-HGG and low-grade-glioma-LGG) patients (p &lt; 0.05, versus control). BCL2L1, GZMB and HLA-A genes were significantly over-expressed in HGG patients (p &lt; 0.05, versus LGG patients). There was positive correlation between the magnitude of fold change of differentially expressed genes in plasma and glioma derived RNA (Spearman r = 0.6344, n = 14, p = 0.017), and with the mean FPKM of TCGA glioma derived RNA samples (Spearman r = 0.4614, n = 19, p = 0.047). There was positive correlation between glioma radiographic tumour burden and the magnitude of fold change of CSF3 gene (r = 0.9813, n = 20, p &lt; 0.001). Conclusions We identified significant differential expression of genes involved in cancer inflammation and immunity among patients with different glioma grades, and we identified positive correlation between the plasma transcriptomic profile and tumour samples, and with TCGA glioma derived RNA.

scholarly journals SURG-32. THE USE OF 5-AMINOLEVULINIC ACID IN LOW-GRADE GLIOMA RESECTION: A SYSTEMATIC REVIEW

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi246-vi246
Author(s):  
Ahmad Almekkawi ◽  
Tarek El Ahmadieh ◽  
Karl Abi-Aad ◽  
Salah Aoun ◽  
Najib EL Tecle ◽  
...  
Keyword(s):  
Systematic Review ◽  
Quality Index ◽  
Aminolevulinic Acid ◽  
High Grade Glioma ◽  
Extent Of Resection ◽  
Low Grade Glioma ◽  
Low Grade ◽  
High Grade ◽  
Visualization Technology ◽  
Glioma Resection

Abstract BACKGROUND 5-aminolevulinic acid is a reliable tool for optimizing high-grade glioma resection. However, its efficacy in low-grade glioma resection remains unclear. OBJECTIVE To study the role of 5-aminolevulinic acid in low-grade glioma resection and assess positive fluorescence rates and effect on the extent of resection. METHODS A systematic review of PubMed, Google Scholar, and Cochrane was performed from the date of inception to February 1, 2019. Studies that correlated 5-aminolevulinic acid fluorescence with low-grade glioma in the setting of operative resection were selected. Studies with biopsy only were excluded. Positive fluorescence rates were calculated. Quality index of the selected papers using the Downs and Black criteria checklist was provided. RESULTS Twelve articles met the selection criteria with 244 histologically-confirmed low-grade glioma patients who underwent microsurgical resection. All patients received 20 mg/kg body weight of 5-aminolevulinic acid. Only 60 patients (n=60/244; 24.5%) demonstrated visual intra-operative 5-aminolevulinic acid fluorescence. The extent of resection was reported in 4 studies, however, the data combined low- and high-grade tumors. Only 2 studies reported on tumor location. Only 3 studies reported on clinical outcomes. The Zeiss OPMI Pentero microscope was most commonly used across all studies. The average quality index was 14.58 (range: 10–17) which correlated with an overall good quality. CONCLUSION There is an overall low correlation between 5-aminolevulinic acid fluorescence and low-grade glioma. Advances in visualization technology and using standardized fluorescence quantification methods may further improve the visualization and reliability of 5-aminolevulinic acid fluorescence in low-grade glioma resection.

scholarly journals Association between small heat shock protein B11 and the prognostic value of MGMT promoter methylation in patients with high-grade glioma

2016 ◽  
Vol 125 (1) ◽  
pp. 7-16 ◽  
Author(s):  
Wen Cheng ◽  
Mingyang Li ◽  
Yang Jiang ◽  
Chuanbao Zhang ◽  
Jinquan Cai ◽  
...  
Keyword(s):  
Heat Shock ◽  
Promoter Methylation ◽  
Messenger Rna ◽  
Prognostic Value ◽  
Methylation Status ◽  
High Grade Glioma ◽  
Low Grade ◽  
High Grade ◽  
Promoter Methylation Status ◽  
Combined Radiochemotherapy

OBJECT This study investigated the role and prognostic value of heat shock proteins (HSPs) in glioma. METHODS Data from 3 large databases of glioma samples (Chinese Glioma Genome Atlas, Repository for Molecular Brain Neoplasia Data, and GSE16011), which contained whole-genome messenger RNA microarray expression data and patients’ clinical data, were analyzed. Immunohistochemical analysis was performed to validate protein expression in another set of 50 glioma specimens. RESULTS Of 28 HSPs, 11 were overexpressed in high-grade glioma (HGG) compared with low-grade glioma. A univariate Cox analysis revealed that HSPB11 has significant prognostic value for each glioma grade, which was validated by a Kaplan-Meier survival analysis. HSPB11 expression was associated with poor prognosis and was independently correlated with overall survival (OS) in HGG. This study further explored the combined role of HSPB11 and other molecular markers in HGG, such as isocitrate dehydrogenase 1 (IDH1) mutation and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. HSPB11 expression was able to refine the prognostic value of IDH1 mutation in patients with HGG. However, when combined with MGMT promoter methylation status, among patients with a methylated MGMT promoter, those with lower levels of HSPB11 expression had longer OS and progression-free survival than patients with higher levels of HSPB11 expression or with an unmethylated MGMT promoter. Moreover, within the MGMT promoter methylation group, patients with low levels of HSPB11 expression were more sensitive to combined radiochemotherapy than those with high levels of HSPB11 expression, which may explain why some patients with HGG with a methylated MGMT promoter show tolerance to radiochemotherapy. CONCLUSIONS HSPB11 was identified as a novel prognostic marker in patients with HGG. Together with MGMT promoter methylation status, HSPB11 expression can predict outcome for patients with HGG and identify those who would most benefit from combined radiochemotherapy.

Brain Tumor Classification into High Grade and Low Grade Gliomas

2019 ◽  
pp. 785-790
Author(s):  
Sanjeet Pandey ◽  
Brijesh Bharadwaj ◽  
Himanshu Pandey ◽  
Vineet Kr. Singh
Keyword(s):  
Invasive Procedure ◽  
High Grade Glioma ◽  
Low Grade Glioma ◽  
World Health ◽  
Low Grade ◽  
High Grade ◽  
Learning Approaches ◽  
Sampling Errors ◽  
Promising Alternative ◽  
Glioma Grading

Brain is recognized as one of the complex organ of the human body. Abnormal formation of cells may affect the normal functioning of the brain. These abnormal cells may belong to category of benign cells resulting in low grade glioma or malignant cells resulting in high grade glioma. The treatment plans vary according to grade of glioma detected. This results in need of precise glioma grading. As per World Health Organization, biopsy is considered to be gold standard in glioma grading. Biopsy is an invasive procedure which may contains sampling errors. Biopsy may also contain subjectivity errors. This motivated the clinician to look for other methods which may overcome the limitations of biopsy reports. Machine learning and deep learning approaches using MRI is considered to be most promising alternative approach reported by scientist in literature. The presented work were based on the concept of AdaBoost approach which is an ensemble learning approach. The developed model was optimized w.r.t to two hyper parameters i.e. no. of estimators and learning rate keeping the base model fixed. The decision tree was us ed as a base model. The proposed developed model was trained and validated on BraTS 2018 dataset. The developed optimized model achieves reasonable accuracy in carrying out classification task i.e. high grade glioma vs. low grade glioma.

Diffusion Weighted Imaging of Brain Gliomas in the Differential Diagnosis Value

2020 ◽  
Author(s):  
Jian JIANG ◽  
Liangcai BAI ◽  
Xueling ZHANG ◽  
Jianli LIU ◽  
Junlin ZHOU
Keyword(s):  
Brain Metastases ◽  
Diffusion Weighted Imaging ◽  
High Grade Glioma ◽  
Low Grade Glioma ◽  
Control Group ◽  
Low Grade ◽  
High Grade ◽  
Imaging Data ◽  
Grade Group ◽  
Diffusion Weighted

Background: To evaluate the diagnostic value of diffusion weighted imaging (DWI) and apparent diffusion coefficient measurement (ADC) in glioma. cient measurement (ADC) in glioma. Methods: Thirty two low-grade glioma patients and 31 high-grade glioma patients who were confirmed by pathology in Lanzhou University Second Hospital, Lanzhou, China from February 2016 to January 2019 were selected. The other 30 patients with brain metastases were selected as a control group. DWI imaging data of the three groups were collected, and ADC, relative ADC (rADC) values in tumor parenchyma, peritumor edema area, and contralateral normal white matter area were measured, and the levels of n-acetyl aspartic acid (NAA), choline (Cho), creatine (Cr) of tumor metabolites were analyzed. Results: rADC values in the peri-tumor edema areas of the high-grade glioma group were significantly lower than those in the low-grade group and the metastatic group （P=0.011）, and the low-grade group was significantly lower than that in the metastatic group (P < 0.05). NAA/Cho and NAA/Cr in parenchymal and peritumor edema areas of patients in the advanced group were significantly lower than those in the metastatic group (P < 0.05), and Cho /Cr was significantly higher than those in the metastatic group (P < 0.05). Conclusion: the rADC value, NAA/Cho, NAA/Cr and Cho/Cr in parenchymal and peritumor edema areas of the tumor can help to distinguish high-grade glioma, low-grade glioma and brain metastases.

Long-term outcomes after irradiation (RT) for pediatric low-grade glioma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 10549-10549
Author(s):  
Derek S. Tsang ◽  
Erin Sennett Murphy ◽  
Thomas E. Merchant
Keyword(s):  
Systemic Therapy ◽  
Cumulative Incidence ◽  
High Grade Glioma ◽  
Tumor Location ◽  
Low Grade Glioma ◽  
Low Grade ◽  
High Grade ◽  
Who Grade ◽  
Extent Of Surgery

10549 Background: Treatment for pediatric low-grade glioma (LGG) is variable, depending on age and tumor location. Systemic therapy (ST) is often used to delay RT, but ST does not result in durable local control. The goal of this study was to evaluate event-free survival (EFS) and toxicities for pediatric LGG treated with RT over a 30-year period. Methods: All patients age ≤21 with intracranial pediatric LGG (WHO grade I-II) treated with RT at a single institution since May 1986 were included in this retrospective review. Patients with metastatic disease (M+) received craniospinal irradiation (CSI); otherwise, RT was conformal. EFS and overall survival (OS) were measured from the first day of RT. Events included death, progression, or secondary high-grade glioma. Results: 221 patients were eligible. Median follow-up was 11.3 yrs (range, 0.1-30.5). Median RT dose was 54 Gy. 10-yr EFS and OS were 67.9% (95% CI 60.4-74.3) and 91.1% (95% CI 85.8-94.5) for non-metastatic patients, respectively. For 12 M+ patients treated with CSI, 10-yr EFS and OS were 58.9% (95% CI 23.4-82.5) and 70.0% (32.9-89.2), respectively. 28.6% developed pseudoprogression (PP) with median time to onset and resolution of 6.1 months (IQR 3.6-14.6) and 6.4 months (IQR 3.5-11.7), respectively. Patients with PP had improved 10-yr EFS (83.4% vs. 61.0%, HR 0.40, p = .006). Patients with grade II tumors and who received pre-RT ST had lower EFS (Table). Sex, NF-1, tumor location, extent of surgery and CSI were not independently associated with EFS. 10-yr cumulative incidence of grade ≥2 vasculopathy was 7.5% (95% CI 4.9-11.4). There were 12 cases of secondary high-grade glioma, with a 20-yr cumulative incidence of 5.5% (95% CI 2.6-11.4). Conclusions: Irradiation provides long-term control of pediatric LGG in a majority of patients. Receipt of pre-RT systemic therapy was associated with reduced EFS; this association requires further investigation. [Table: see text]

Temozolomide after Radiotherapy for Newly Diagnosed High-grade Glioma and Unfavorable Low-grade Glioma in Children

2005 ◽  
Vol 76 (3) ◽  
pp. 313-319 ◽  
Author(s):  
Alberto Broniscer ◽  
Murali Chintagumpala ◽  
Maryam Fouladi ◽  
Matthew J. Krasin ◽  
Mehmet Kocak ◽  
...  
Keyword(s):  
High Grade Glioma ◽  
Low Grade Glioma ◽  
Low Grade ◽  
High Grade ◽  
Newly Diagnosed
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