scholarly journals Potential Diagnostic Value of the Differential Expression of Histone H3 Variants between Low- and High-Grade Gliomas

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5261
Author(s):  
Irati Hervás-Corpión ◽  
Andrea Gallardo-Orihuela ◽  
Inmaculada Catalina-Fernández ◽  
Irene Iglesias-Lozano ◽  
Olga Soto-Torres ◽  
...  

Glioblastoma (GB) is the most aggressive form of glioma and is characterized by poor prognosis and high recurrence despite intensive clinical interventions. To retrieve the key factors underlying the high malignancy of GB with potential diagnosis utility, we combined the analysis of The Cancer Gene Atlas and the REMBRANDT datasets plus a molecular examination of our own collection of surgical tumor resections. We determined a net reduction in the levels of the non-canonical histone H3 variant H3.3 in GB compared to lower-grade astrocytomas and oligodendrogliomas with a concomitant increase in the levels of the canonical histone H3 variants H3.1/H3.2. This increase can be potentially useful in the clinical diagnosis of high-grade gliomas, as evidenced by an immunohistochemistry screening of our cohort and can be at least partially explained by the induction of multiple histone genes encoding these canonical forms. Moreover, GBs showing low bulk levels of the H3.1/H3.2 proteins were more transcriptionally similar to low-grade gliomas than GBs showing high levels of H3.1/H3.2. In conclusion, this study identifies an imbalanced ratio between the H3 variants associated with glioma malignancy and molecular patterns relevant to the biology of gliomas, and proposes the examination of the H3.3 and H3.1/H3.2 levels to further refine diagnosis of low- and high-grade gliomas in future studies.

2020 ◽  
Vol 79 (10) ◽  
pp. 1038-1043
Author(s):  
Meaghan Morris ◽  
Meghan Driscoll ◽  
John W Henson ◽  
Charles Cobbs ◽  
LiQun Jiang ◽  
...  

Abstract Mutations in histone H3 are key molecular drivers of pediatric and young adult high-grade gliomas. Histone H3 G34R mutations occur in hemispheric high-grade gliomas and H3 K27M mutations occur in aggressive, though histologically diverse, midline gliomas. Here, we report 2 rare cases of histologically low-grade gliomas with gemistocytic morphology and sequencing-confirmed histone H3 G34R mutations. One case is a histologically low-grade gemistocytic astrocytoma with a G34R-mutation in H3F3A. The second case is a histologically low-grade gemistocytic astrocytoma with co-occurring K27M and G34R mutations in HIST1H3B. Review of prior histone H3-mutant gliomas sequenced at our institution shows a divergent clinical and immunohistochemical pattern in the 2 cases. The first case is similar to prior histone H3 G34R-mutant tumors, while the second case most closely resembles prior histone H3 K27M-mutant gliomas. These represent novel cases of sequencing-confirmed histone H3 G34R-mutant gliomas with low-grade histology and add to the known rare cases of G34R-mutant tumors with gemistocytic morphology. Although K27M and G34R mutations are thought to be mutually exclusive, we document combined K27M and G34R mutations in HIST1H3B and present evidence suggesting the K27M-mutation drove tumor phenotype in this dual mutant glioma.


2021 ◽  
pp. 1-8
Author(s):  
Haimei Cao ◽  
Xiang Xiao ◽  
Jun Hua ◽  
Guanglong Huang ◽  
Wenle He ◽  
...  

Objectives: The present study aimed to study whether combined inflow-based vascular-space-occupancy (iVASO) MR imaging (MRI) and diffusion-weighted imaging (DWI) improve the diagnostic accuracy in the preoperative grading of gliomas. Methods: Fifty-one patients with histopathologically confirmed diffuse gliomas underwent preoperative structural MRI, iVASO, and DWI. We performed 2 qualitative consensus reviews: (1) structural MR images alone and (2) structural MR images with iVASO and DWI. Relative arteriolar cerebral blood volume (rCBVa) and minimum apparent diffusion coefficient (mADC) were compared between low-grade and high-grade gliomas. Receiver operating characteristic (ROC) curve analysis was performed to compare the tumor grading efficiency of rCBVa, mADC, and the combination of the two parameters. Results: Two observers diagnosed accurate tumor grade in 40 of 51 (78.4%) patients in the first review and in 46 of 51 (90.2%) in the second review. Both rCBVa and mADC showed significant differences between low-grade and high-grade gliomas. ROC analysis gave a threshold value of 1.52 for rCBVa and 0.85 × 10−3 mm2/s for mADC to provide a sensitivity and specificity of 88.0 and 81.2% and 100.0 and 68.7%, respectively. The area under the ROC curve (AUC) was 0.87 and 0.85 for rCBVa and mADC, respectively. The combination of rCBVa and mADC values increased the AUC to 0.92. Conclusion: The combined application of iVASO and DWI may improve the diagnostic accuracy of glioma grading.


2021 ◽  
Author(s):  
Xin Jia ◽  
Yixuan Zhai ◽  
Fengdong Yang ◽  
Yiming Wang ◽  
Shuxin Wei ◽  
...  

Abstract Objective The purpose of our study is to explore the diagnostic value of the single and combined hematological maker for the classification and isocitrate dehydrogenase (IDH)-1/2 mutations molecular subtypes of high-grade gliomas (HGGs). Methods A total of 354 newly diagnosed HGGs patients were included in this study. Firstly, we compared the levels of hematology indicators in the classification and molecular subtypes of HGGs. Next, the correlation between the levels of hematology indicators with basic clinical features was analyzed. Finally, the diagnostic value of the single and combined hematology indicator for identifying the classification and molecular subtypes from HGGs was performed. Results The level of fibrinogen (FIB) was higher in higher grade gliomas and glioblastoma multiforme IDH wild type (GBM IDH-wt). Nutrition-related indicators such as serum albumin (ALB), albumin/globulin ratio (AGR), and prognostic nutrition index (PNI) were negatively correlated with age, whereas FIB was positively associated with age. Compared with women, men with GBM had significantly higher AGR and lower serum globulin (GLOB). We found that the best single and combined indicator for identifying GBM and GBM IDH-wt from HGGs were FIB [0.595 (0.519–0.672) and 0.615 (0.546–0.684)] and age + FIB [0.712 (0.642–0.783) and 0.726 (0.662–0.791)], respectively. Conclusions Preoperative hematological indicators have high diagnostic value for GBM and GBM IDH-wt from HGGs, especially FIB combined age.


2021 ◽  
pp. 21-24
Author(s):  
A. V. Fedorova ◽  
N. V. Kochergina ◽  
A. B. Bludov ◽  
I. V. Boulycheva ◽  
E. A. Sushentsov ◽  
...  

Purpose. Determining the diagnostic value of magnetic resonance imaging in the accurate definition of chondrosarcoma of bone grade at the pre-surgery examination. Material and methods. We analyzed examination data (magnetic resonance imaging with no contrast enhancement) of 70 patients with chondrosarcoma (35 patients with low-grade chondrosarcoma and 35 patients with high grade chondrosarcoma). Informative weighted coefficients were determined separately for ‘learning’ and ‘examination’ samples. On the basis of weighted coefficients, the decisive rule was created for differentiation between low-grade and high-grade chondrosarcoma. Results. The sensitivity of the method was 87.0%, specificity was 95.6%, total correct classification was 91.03%. Conclusion. Magnetic resonance imaging is a highly informative method for prediction of chondrosarcoma grade at the pre-surgery examination.


2016 ◽  
Vol 29 (5) ◽  
pp. 400-407 ◽  
Author(s):  
Lamiaa El-Serougy ◽  
Ahmed Abdel Khalek Abdel Razek ◽  
Amani Ezzat ◽  
Hany Eldawoody ◽  
Ahmad El-Morsy

2018 ◽  
Vol 38 (3) ◽  
Author(s):  
Li-qiang Liu ◽  
Li-fei Feng ◽  
Cheng-rui Nan ◽  
Zong-mao Zhao

The present study was conducted to investigate the clinical significance of cAMP responsive element binding protein 3 like 1 (CREB3L1) and pleiotrophin (PTN) expression in prognosis of patients with brain gliomas. Human brain tissue samples were collected from normal glial tissues (control), low- and high-grade glioma tissues. CREB3L1 and PTN expression levels in cells were assessed by immunohistochemistry (IHC), and population distribution of the CREB3L1- and PTN-presenting patients was examined. The CREB3L1 and PTN mRNA expression levels in three types of the brain cells was determined by RT-PCR. Survival rates for population of the CREB3L1- and PTN-presenting patients were examined. CREB3L1+ cell counts were decreased with increased PTN+ cells in the low-grade and high-grade glioma tissues as compared with the control. Population proportion of the CREB3L1+-presenting patients decreased from the control to the high-grade glioma and the population of the PTN+-presenting patients increased in low- and high-grade gliomas as compared with the control (both P<0.05). The decrease in the CREB3L1 mRNA expression was associated with the increase in the PTN mRNA expression in the low- and high-grade gliomas (P<0.05). Survival time for patients with CREB3L1− and PTN+ gliomas was shorter than patients with CREB3L1+ and PTN− gliomas in the investigated cohorts (both P<0.05). There was a relationship between the expression levels of both proteins and survival time. CREB3L1 and PTN expression levels serve as biomarkers with utility in grading gliomas. Absence of CREB3L1 and presence of PTN in brain glioma cells correlate with survival time of the glioma patients.


2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Yuankai Lin ◽  
Jianrui Li ◽  
Zhiqiang Zhang ◽  
Qiang Xu ◽  
Zhenyu Zhou ◽  
...  

Gliomas grading is important for treatment plan; we aimed to investigate the application of intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) in gliomas grading, by comparing with the three-dimensional pseudocontinuous arterial spin labeling (3D pCASL). 24 patients (13 high grade gliomas and 11 low grade gliomas) underwent IVIM DWI and 3D pCASL imaging before operation; maps of fast diffusion coefficient (D∗), slow diffusion coefficient (D), fractional perfusion-related volume (f), and apparent diffusion coefficient (ADC) as well as cerebral blood flow (CBF) were calculated and then coregistered to generate the corresponding parameter values. We found CBF andD∗were higher in the high grade gliomas, whereas ADC,D, andfwere lower (allP<0.05). In differentiating the high from low grade gliomas, the maximum areas under the curves (AUC) ofD∗, CBF, and ADC were 0.857, 0.85, and 0.902, respectively. CBF was negatively correlated withfin tumor (r=-0.619,P=0.001). ADC was positively correlated withDin both tumor and white matter (r=0.887,P=0.000andr=0.824,P=0.000, resp.). There was no correlation between CBF andD∗in both tumor and white matter (P>0.05). IVIM DWI showed more efficiency than 3D pCASL but less validity than conventional DWI in differentiating the high from low grade gliomas.


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