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 ◽  
...  

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 < 0.05, versus control). BCL2L1, GZMB and HLA-A genes were significantly over-expressed in HGG patients (P < 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 < 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.

2021 ◽  
Vol 108 (Supplement_6) ◽  
Author(s):  
M Ita ◽  
J H Wang ◽  
A Toulouse ◽  
C Lim ◽  
N Fanning ◽  
...  

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 < 0.05, versus control). BCL2L1, GZMB and HLA-A genes were significantly over-expressed in HGG patients (p < 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 < 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.


Author(s):  
Michael Itak Ita ◽  
Jiang Huai Wang ◽  
André Toulouse ◽  
Chris Lim ◽  
Noel Fanning ◽  
...  

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.


2016 ◽  
Vol 125 (1) ◽  
pp. 7-16 ◽  
Author(s):  
Wen Cheng ◽  
Mingyang Li ◽  
Yang Jiang ◽  
Chuanbao Zhang ◽  
Jinquan Cai ◽  
...  

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.


1972 ◽  
Vol 71 (2_Suppla) ◽  
pp. S369-S380 ◽  
Author(s):  
Francis T. Kenney ◽  
Kai-Lin Lee ◽  
Charles D. Stiles

ABSTRACT Analyses of the response of hydrocortisone-induced tyrosine transaminase in cultured H-35 cells to inhibitors of translation (cycloheximide, puromycin) suggest: (1) that bound ribosomes stabilize messenger RNA in vivo; (2) that messenger is degraded at a rate determined by the rate of translation. Since specific messenger RNAs of mammalian cells are degraded at quite different rates, there may be extensive heterogeneity either in the rate at which ribosomes traverse different messengers or in the number of ribosomes which translate specific messenger RNAs.


2021 ◽  
Author(s):  
Roi Tschernichovsky ◽  
Lior H Katz ◽  
Estela Derazne ◽  
Matan Ben-Zion Berliner ◽  
Maya Simchoni ◽  
...  

Abstract Background Gliomas manifest in a variety of histological phenotypes with varying aggressiveness. The etiology of glioma remains largely unknown. Taller stature in adulthood has been linked with glioma risk. The aim of this study was to discern whether this association can be detected in adolescence. Methods The cohort included 2,223,168 adolescents between the ages of 16-19. Anthropometric measurements were collected at baseline. Incident cases of glioma were extracted from the Israel National Cancer Registry over a follow-up period spanning 47,635,745 person-years. Cox proportional hazard models were used to estimate the hazard ratio for glioma and glioma subtypes according to height, body mass index (BMI) and sex. Results 1,195 patients were diagnosed with glioma during the study period. Mean(SD) age at diagnosis was 38.1 (11.7) years. Taller adolescent height (per 10cm increase) was positively associated with the risk for glioma of any type (HR 1.15; p=0.002). The association was retained in subgroup analyses for low-grade glioma (HR 1.17; p=0.031), high-grade glioma (HR 1.15; p=0.025), oligodendroglioma (HR 1.31; p=0.015), astrocytoma (HR 1.12; p=0.049), and a category of presumed IDH-mutated glioma (HR 1.17; p=0.013). There was a trend towards a positive association between height and glioblastoma, however this had borderline statistical significance (HR: 1.15; p=0.07). After stratification of the cohort by sex, height remained a risk factor for men, but not for women. Conclusions The previously - established association between taller stature in adulthood and glioma risk can be traced back to adolescence. The magnitude of association differs by glioma subtype.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Indrawati Hadi ◽  
Daniel Reitz ◽  
Raphael Bodensohn ◽  
Olarn Roengvoraphoj ◽  
Stefanie Lietke ◽  
...  

Abstract Purpose Frequency and risk profile of radiation necrosis (RN) in patients with glioma undergoing either upfront stereotactic brachytherapy (SBT) and additional salvage external beam radiotherapy (EBRT) after tumor recurrence or vice versa remains unknown. Methods Patients with glioma treated with low-activity temporary iodine-125 SBT at the University of Munich between 1999 and 2016 who had either additional upfront or salvage EBRT were included. Biologically effective doses (BED) were calculated. RN was diagnosed using stereotactic biopsy and/or metabolic imaging. The rate of RN was estimated with the Kaplan Meier method. Risk factors were obtained from logistic regression models. Results Eighty-six patients (49 male, 37 female, median age 47 years) were included. 38 patients suffered from low-grade and 48 from high-grade glioma. Median follow-up was 15 months after second treatment. Fifty-eight patients received upfront EBRT (median total dose: 60 Gy), and 28 upfront SBT (median reference dose: 54 Gy, median dose rate: 10.0 cGy/h). Median time interval between treatments was 19 months. RN was diagnosed in 8/75 patients. The 1- and 2-year risk of RN was 5.1% and 11.7%, respectively. Tumor volume and irradiation time of SBT, number of implanted seeds, and salvage EBRT were risk factors for RN. Neither of the BED values nor the time interval between both treatments gained prognostic influence. Conclusion The combination of upfront EBRT and salvage SBT or vice versa is feasible for glioma patients. The risk of RN is mainly determined by the treatment volume but not by the interval between therapies.


2020 ◽  
Vol 2 (Supplement_3) ◽  
pp. ii12-ii13
Author(s):  
Shinichiro Koizumi ◽  
Kazuhiko Kurozumi

Abstract Introduction: The elasticity of intracranial tumors is difficult to assess non-invasively because the lesion is surrounded by the skull. Therefore, intracranial tumors have not been verified before surgery in terms of elastic modulus. Magnetic resonance elastography (MRE) is an epoch-making method capable of non-invasively imaging the elasticity of internal organs. We have examined the elasticity of meningiomas and pituitary adenomas and reported their usefulness. This time, we measured the glioma elasticity and verified usefulness of MRE. Method: Twenty-four gliomas (mean age 51.8±15.7 years, male: female = 17: 7) who underwent tumor resection after MRE imaging from July 2017 to May 2020 were targeted. The average elasticity was measured as an evaluation of tumor elastic modulus by MRE. Gliomas were divided into a low-grade glioma group (LGG: Grade 1, 2) and a high-grade glioma group (HGG: Grade 3, 4). Then, a comparative statistical study was conducted. Results: The average values of the average elasticity of LGG group (9 cases) and HGG group (15 cases) were 1.8±0.8 kPa and 2.5±0.8 kPa, respectively. The average elasticity was significantly higher in the HGG group (p=0.023). In the ROC analysis, the cutoff value was 2.1 kPa (sensitivity 70%, specificity 70%). Therefore, it was suggested that the tumor is likely to be HGG when the average elasticity is 2.1 kPa or more. Discussion: The glioma elasticity by preoperative MRE was significantly higher in the HGG group. Based on actual surgical experience, the tumor seems to be hard in the HGG group, and it was judged to be consistent with this our MRE research. The preoperative evaluation of glioma elasticity by MRE was considered useful, and it might help in planning a surgical strategy considering malignant grade.


2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii357-iii358
Author(s):  
Ioan Paul Voicu ◽  
Antonio Napolitano ◽  
Alessia Carboni ◽  
Lorenzo Lattavo ◽  
Andrea Carai ◽  
...  

Abstract PURPOSE To develop a predictive grading model based on diffusion kurtosis imaging (DKI) metrics in children affected by gliomas, and to investigate the clinical impact of the model via correlations with overall survival and progression-free survival. MATERIALS AND METHODS We retrospectively studied 59 children (33M, 26F, median age 7.2 years) affected by gliomas on a 3T magnet. Patients with tumor locations other than infratentorial midline were included. Conventional and DKI sequences were obtained. Mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), fractional anisotropy (FA) and apparent diffusion coefficient (ADC) maps were obtained. Whole tumor volumes (VOIs) were segmented semiautomatically. Mean DKI values were calculated for each metric. The quantitative values from DKI-derived metrics were used to develop a predictive grading model with penalized logistic regression (glmnet package, R). Elasticnet regularization was used to avoid model overfitting. Fitted model coefficients from each metric were used to develop a probability prediction of a high-grade glioma (HGG). Grading accuracy of the resulting probabilities was tested with ROC analysis. Finally, model predictions were correlated to progression-free survival (PFS) with a Kaplan-Meier analysis. RESULTS The cohort included 46 patients with low-grade gliomas (LGG) and 13 patients with HGG. The developed model predictions yielded an AUC of 0.946 (95%CI: 0.890–1). Model predictions were significantly correlated with PFS (23.1 months for HGG vs 34.7 months for LGG, p&lt;0.004). CONCLUSION In our cohort, a DKI-based predictive model was highly accurate for pediatric glioma grading. DKI-based model predictions were significantly correlated with progression-free survival.


2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii346-iii346
Author(s):  
Tamaki Morisako ◽  
Daisuke Umebayashi ◽  
Kazuaki Kamata ◽  
Hiroyuki Yamamoto ◽  
Takumi Yamanaka ◽  
...  

Abstract INTRODUCTION Tumors arising from the spinal cord are uncommon, especially high-grade tumors in pediatric patients. We report a case of high-grade glioma in the spinal cord harboring NTRK1 gene fusion, who received effective entrectinib therapy. CASE REPORT: A 5-year-old boy presented right hemiparesis and MR imaging revealed an intramedullary enhancing mass at the vertebral body level between C3 and Th1. He underwent microsurgical partial resection and the histological diagnosis was low-grade astrocytoma. After the first-line chemotherapy with vincristine and carboplatin, his right hemiparesis deteriorated and recurrent MR imaging showed growth of the tumor. He underwent microsurgical partial resection again and the histological examination was high-grade glioma with endothelial proliferation and necrosis. The chemoradiotherapy with temozolomide and focal irradiation of 50.4 Gy were given, and his neurological symptom slightly improved. One month later, he presented respiratory disturbance and required assisted ventilation with tracheostomy. MR imaging showed tumor progression invading upward to medulla oblongata. NTRK1 gene fusion was detected in the previous surgical specimen by a gene panel testing, and he received entrectinib, a potent inhibitor of tropomyosin receptor kinase (TRK). Since then, no tumor progression has been demonstrated for several months by MRI and he has been stable neurologically. CONCLUSION High-grade spinal cord tumors are rare and effective treatment strategies have not been addressed. Although the frequency of the gene fusion is very low in pediatric gliomas, identification of the driver gene aberration like in this case by a gene panel can provide potential targeted therapies for selected patients.


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