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Glioblastoma is one of the most frequent primary brain tumors with a poor prognosis. Nevertheless, some patients show a prolonged survival. The aim of the present study was to compare the expression profiles of tumor derived microRNA (miR) of long‑term survivors with those of short‑term survivors in order to identify differentially expressed miRs as well as their target genes, which may elucidate mechanisms that play a role in varying tumor progression and, therefore, may influence survival. Formalin‑fixed paraffin‑embedded samples of 23 patients with glioblastoma were classified according to overall survival. Profiles of miR expression were determined using Nanostring technology. Expression levels of potential target genes of differentially expressed miRs were assessed using immunohistochemistry. MiR profiles of long‑term survivors differed from those of short‑term survivors. A total of three prominent differentially expressed miRs were highlighted: MiR‑130b‑3p, which is downregulated in long‑term survivors, and miR‑146b‑5p and miR‑148a‑3p, which are upregulated in long‑term survivors. Known tumor suppressor genes are among targets potentially affected by miR‑130b‑3p, whereas targets of miR‑146b‑5p and miR‑148a‑3p consist of several genes known to have a role in tumor invasion and aggressiveness. In conclusion, it was revealed that a type of miR‑signature was associated with short‑ and long‑term survival, potentially serving as biomarker for disease progression and providing a base for further functional studies.

Glioblastoma (GBM) is one of the most frequent primary brain tumors. Limited therapeutic options and high recurrency rates lead to a dismal prognosis. One frequent, putative driver mutation is the genomic amplification of the oncogenic receptor tyrosine kinase EGFR. Often accompanied by variants like EGFRvIII, heterogenous expression and ligand independent signaling render this tumor subtype even more difficult to treat, as EGFR-directed therapeutics show only weak effects at best. So EGFR-amplified GBM is considered to have an even worse prognosis, and therefore, deeper understanding of molecular mechanisms and detection of potential targets for novel therapeutic strategies is urgently needed. In this study, we looked at the level of microRNAs (miRs), small non-coding RNAs frequently deregulated in cancer, both acting as oncogenes and tumor suppressors. Comparative analysis of GBM with and without EGFR amplification should give insight into the expression profiles of miRs, which are considered both as potential targets for directed therapies or as therapeutic reagents. Comparison of miR profiles of EGFR-amplified and EGFR-normal GBM revealed an upregulation of the miR-183/96/182 cluster, which is associated with oncogenic properties in several tumor entities. One prominent target of this miR cluster is FOXO1, a pro-apoptotic factor. By observing FOXO1 downregulation in EGFR-amplified tumors, we can see a significant correlation of EGFR amplification, miR-183/96/182 cluster upregulation, and repression of FOXO1. Although no significant difference in overall survival is shown, these data may contribute to the molecular understanding of this tumor subtype and offer potential targets for miR-based therapies., (© 2022. The Author(s).)

Gliomas are the most common primary brain tumors and often become apparent through symptomatic epileptic seizures. Glial cells express the inwardly rectifying K + channel Kir4.1 playing a major role in K + buffering, and are presumably involved in facilitating epileptic hyperexcitability. We therefore aimed to investigate the molecular and functional expression of Kir4.1 channels in cultured rat and human glioma cells. Quantitative PCR showed reduced expression of Kir4.1 in rat C6 and F98 cells as compared to control. In human U-87MG cells and in patient-derived low-passage glioblastoma cultures, Kir4.1 expression was also reduced as compared to autopsy controls. Testing Kir4.1 function using whole-cell patch-clamp experiments on rat C6 and two human low-passage glioblastoma cell lines (HROG38 and HROG05), we found a significantly depolarized resting membrane potential (RMP) in HROG05 (-29 ± 2 mV, n = 11) compared to C6 (-71 ± 1 mV, n = 12, P < 0.05) and HROG38 (-60 ± 2 mV, n = 12, P < 0.05). Sustained K + inward or outward currents were sensitive to Ba 2+ added to the bath solution in HROG38 and C6 cells, but not in HROG05 cells, consistent with RMP depolarization. While immunocytochemistry confirmed Kir4.1 in all three cell lines including HROG05, we found that aquaporin-4 and Kir5.1 were also significantly reduced suggesting that the Ba 2+ -sensitive K + current is generally impaired in glioma tissue. In summary, we demonstrated that glioma cells differentially express functional inwardly rectifying K + channels suggesting that impaired K + buffering in cells lacking functional Ba 2+ -sensitive K + currents may be a risk factor for increased excitability and thereby contribute to the differential epileptogenicity of gliomas., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Seizures are a common initial symptom of malignant brain tumors such as glioblastoma (GBM). However, why some of these tumors are epileptogenic and others never trigger seizures remains controversial., Objective: To identify potential clinical and radiological features of epileptogenic tumors and the effect of initial seizures on survival., Methods: The analyzed patient cohort was retrospectively compiled (bicentric), only isocitrate dehydrogenase wild-type GBMs were included. Volumetric assessment was performed on pretreatment magnetic resonance imaging with the aid of a semi-automated 3D measurement (tumor, necrosis, and edema volume). Two ratios were calculated, reflecting the proportion of peritumoral edema and necrosis (NTR) toward the tumor volume. For overall survival analyses, only patients after a surgical resection (residual tumor volume <2 cm3) followed by standard radiation and chemotherapy were included., Results: Pretreatment seizures occurred in 33% of cases (n = 224), younger patients (≤60 yr) were predominantly affected (P = .022). All measured volumes were inversely correlated with the onset of seizures (P = .001). In multivariate analyses, the total tumor volume and the NTR were considerably smaller within epileptogenic GBMs (P = .050, P = .019, respectively). A positive statin intake was associated with significantly lesser seizure (P = .007, odds ratio 4.94). Neither the occurrence of seizures nor the intake of statins had an impact on OS (P = .357, P = .507, respectively)., Conclusion: The size and amount of necrosis was significantly smaller in epileptogenic GBMs, maybe owed to the fact that these tumors were clinically detected at an earlier stage of their growth. Furthermore, the intake of statins was associated with a decreased occurrence of pretreatment seizures., (Copyright © 2019 by the Congress of Neurological Surgeons.)

Background: The objective of this study was to evaluate the morphology of glioblastoma on structural pretreatment magnetic resonance imaging (MRI), defining imaging prognostic factors., Method: We conducted a retrospective analysis of MR images from 114 patients harboring a primary glioblastoma, derived from two neurosurgical departments. Tumor segmentation was carried out in a semi-automated fashion. Tumor compartments comprised contrast-enhancing volume (CEV+), perifocal hyperintensity on fluid-attenuated inversion recovery (FLAIR) images (FLAIR+) excluding CEV+, and a non-enhancing area within the CEV+ lesion (CEV-). Additionally, two ratios were calculated from these volumes, the edema-tumor ratio (ETR) and necrosis-tumor ratio (NTR). All patients received surgical resection, followed by concomitant radiation and chemotherapy., Results: Tumor segmentation revealed the strongest correlation between the CEV+ volume and the CEV-, presenting intratumoral necrosis (p < 0.001). The relation between the tumor surrounding the FLAIR+ area and the CEV+ volume and the ETR is inversely correlated (p = 0.001). The most important prognostic factor in multivariable analysis was NTR (HR 2.63, p = 0.016). The cut-off value in our cohort for NTR was 0.33, equivalent to a decrease in survival if the necrotic core of the tumor (CEV-) accounts for more than 33% of the tumor mass itself (CEV+)., Conclusions: Our data emphasizes the importance of the necrosis-tumor ratio as a biomarker in glioblastoma imaging, rather than single tumor compartment volumes. NTR can help to identify a subset of tumors with a higher resistance to therapy and a dismal prognosis.

Objective: Previous research has shown a strong correlation between the Ki-67 proliferation index and grade of malignancy in astrocytoma. Ki-67 has also shown encouraging results as a prognostic marker for patients' overall survival (OS). We focus on whether the index is linked to the appearance of glioblastoma on pretreatment magnetic resonance imaging (MRI) or to OS., Methods: In our retrospective study, only isocitrate dehydrogenase IDH wild-type glioblastoma was included (n = 152). Ki-67 index was quantified via immunohistochemistry. On all pretreatment MRI, tumor compartments (tumor, necrosis, and edema) were volumetrically assessed. An OS subpopulation was filtered from the total cohort (residual tumor volume ≤2 cm 3 ). In addition, a propensity score matching was executed., Results: All volumetric assessed tumor volumes correlated with each other (P ≤ 0.011), although the Ki-67 index showed no correlation with any of the measured volumes. Concerning the OS, a cutoff value of 20% for the Ki-67 index showed a significant influence on patients' OS in multivariate analysis (P = 0.043)., Conclusions: The unique appearance of every glioblastoma on MRI seems to be independent of the Ki-67 index. Furthermore, the Ki-67 index did show a distinct prognostic value for OS within our cohort at a cutoff value of 20% for Ki-67., (Copyright © 2019 Elsevier Inc. All rights reserved.)

There is a distinct diversity between the appearance of every glioblastoma multiforme (GBM) on pretreatment magnetic resonance imaging (MRI) with a potential impact on clinical outcome and survival of the patients. The object of this study was to determine the impact of 10 different single nucleotide polymorphisms (SNPs) on various volumetric parameters in patients harboring a GBM. We prospectively analyzed 20 steroid-naïve adult patients who had been treated for newly diagnosed GBM. The volumetry was performed using MRI with the help of a semiautomated quantitative software measuring contrast enhancing tumor volume including necrosis, central necrosis alone and peritumoral edema (PTE). We calculated ratios between the tumor volume and edema (ETR), respectively necrosis (NTR). SNP analysis was done using genomic DNA extracted from peripheral blood genotyped via PCR and sequencing. There was a strong correlation between tumor volume and PTE (p < 0.001), necrosis (p < 0.001) and NTR (p = 0.003). Age and sex had no influence on volumetric data. The Aquaporin 4-31G > A SNP had a significant influence on the ETR (p = 0.042) by decreasing the measured edema compared with the tumor volume. The Interleukin 8-251A > T SNP was significantly correlated with an increased tumor (p = 0.048), PTE (p = 0.033) and necrosis volume (p = 0.028). We found two SNPs with a distinct impact on pretreatment tumor characteristics, presenting a potential explanation for the individual diversity of GBM appearance on MRI and influence on survival.