The Prognostic Role of Peritumoral Edema in Patients with Newly Diagnosed Glioblastoma: A Retrospective Analysis.

OBJECTIVE: Previous studies on glioblastomas (GBMs) have not reached a consensus on peritumoral edema (PTE)'s influence on survival. This study evaluated the PTE index's prognostic role in newly diagnosed GBMs using a well-designed method. METHODS: Selected patients were reviewed after a rigorous screening process. Their general information was obtained from electronic medical records. The imaging metrics (MTD, TTM, TTE) representing tumor diameter, laterality, and PTE extent were obtained by manual measurement in Syngo FastView software. The PTE index was a ratio of TTE to MTD. Multiple variables were evaluated using analysis of variance and Cox regression model. RESULTS: Of 143 patients, 62 were included in this study. MGMT promoter methylation and tumor laterality were both independent prognostic factors (p = 0.020, 0.042; HR = 0.272, 2.630). The lateral tumors' index was higher than that of the medial tumors (57.7% vs. 42.6%, p = 0.027). Low-index tumors were located in relatively medial positions compared with high-index tumors (TTM, 4.9 vs. 12.8, p = 0.032). This finding indicated that the PTE index tended to increase with tumor laterality. Moreover, the patients with low-index tumors had a significant survival disadvantage in the univariate analysis but not in the multivariate analysis (p = 0.023, 0.220). However, further analysis found that the combination of tumor laterality and PTE statistically stratified the survival outcome. The patients with lateral high-index tumors survived significantly longer (p = 0.022, HR = 1.927). CONCLUSIONS: In contrast with the previous studies, this study recommends combining PTE and tumor laterality for survival stratification in newly diagnosed GBMs.

The Associations Between Preoperative Conventional MRI Features and Genetic Biomarkers Status in Newly Diagnosed GBMs: A Clinical Summary and Prognostic Analysis.

AIM: To analyze certain magnetic resonance imaging (MRI) features as well as six major genetic biomarkers, investigated their associations, and evaluated their prognostic roles in glioblastomas (GBMs). MATERIAL AND METHODS: Strict criteria included newly diagnosed GBM with optimal treatments. Simple manual imaging characteristics (tumor side, location, enhancement, diameter, depth, radiographic necrosis, and edema) were obtained from preoperative conventional MRI. Furthermore, all the status of the MGMT promoter, Chromosome 1p and 19q, IDH, TERT, and BRAF in tumor tissues were detected. RESULTS: Among 126 inpatients, 60 cases were selected and enrolled in the study. The status of the MGMT promoter was significantly associated with the grade of radiographic necrosis (p=0.033). The rate of 19q deletion was significantly higher in tumors with the ring-shaped peritumoral edema (PTE) (p=0.035) and in tumors with the ring-enhanced trait (p=0.023). Univariate analysis showed that a low PTE index and MGMT promoter methylation were both unfavorable prognostic factors. While the PTE index statistically dropped out, the status of the MGMT promoter and the depth of the tumor were observed to be independent prognostic factors in multivariate analysis. CONCLUSION: Based on simple neuroimaging metrics, novel connections between features of preoperative conventional MRI and status of major genetic biomarkers were observed, especially for the MGMT promoter and 19q.

TRIM24 promotes stemness and invasiveness of glioblastoma cells via activating Sox2 expression.

BACKGROUND: Glioblastoma stem cells (GSCs) are a subpopulation of glioblastoma (GBM) cells that are critical for tumor invasion and treatment resistance. However, little is known about the function and mechanism of tripartite motif-containing 24 (TRIM24) in GSCs. METHODS: Immunofluorescence, flow cytometry, and western blot analyses were used to evaluate TRIM24 and cluster of differentiation (CD)133 expression profiles in GBM surgical specimens and GSC tumorspheres. Different TRIM24 expression levels in patients' tumors, as measured by both immunohistochemistry and western blot, were related to their corresponding MRI data. Wound healing, Matrigel invasion, and xenograft immunohistochemistry were conducted to determine GBM cell invasion. RESULTS: We identified that TRIM24 was coexpressed with CD133 and Nestin in GBM tissues and tumorsphere cells. Limiting dilution assays and xenotransplantation experiments illustrated that knockdown of TRIM24 expression reduced GSC self-renewal capacity and invasive growth. TRIM24 expression levels were positively associated with the volumes of peritumoral T2 weighted image abnormality. Rescue experiments indicated TRIM24 participation in GBM infiltrative dissemination. Chromatin immunoprecipitation, reporter gene assay, PCR, western blot, and immunohistochemistry demonstrated that TRIM24 activated the expression of the pluripotency transcription factor sex determining region Y-box 2 (Sox2) to regulate GBM stemness and invasion in vitro and in vivo. Finally, the close relationship between TRIM24 and Sox2 was validated by testing samples enrolled in our study and exploring external databases. CONCLUSIONS: Our findings uncover essential roles of the TRIM24-Sox2 axis in GBM stemness and invasiveness, suggesting TRIM24 as a potential target for effective GBM management.