Search Results (94)

Pediatric high-grade glioma (pHGG) is a devastating group of childhood cancers associated with poor outcomes. Traditionally, diagnosis was based on histologic and immunohistochemical characteristics, including high mitotic activity, presence of necrosis, and presence of glial cell markers (e.g., GFAP). With advances in molecular tumor profiling, these tumors have been recategorized based on specific molecular findings that better lend themselves to prediction of treatment response and prognosis. pHGG is now categorized into four subtypes: H3K27-altered, H3G34-mutant, H3/IDH-WT, and infant-type high-grade glioma (iHGG). Molecular profiling has not only increased the specificity of diagnosis but also improved prognostication. Additionally, these molecular findings provide novel targets for individual tumor-directed therapy. While these therapies are largely still under investigation, continued investigation of distinct molecular markers in these tumors is imperative to extending event-free survival (EFS) and overall survival (OS) for patients with pHGG. Full article

Background/Objectives: This study evaluates intratumoral susceptibility signals (ITSS) as imaging markers for glioma grade prediction and their association with molecular and histopathologic features, in the context of the fifth edition of the World Health Organization Classification of Tumors of the Central Nervous System (WHO CNS5). Methods: We retrospectively analyzed patients with adult diffuse gliomas who underwent pretreatment magnetic resonance imaging. ITSS were semiquantitatively graded by two radiologists: grade 0 (no signal), grade 1 (1–5), grade 2 (6–10), and grade 3 (≥11). Relative cerebral blood volume (rCBV) and tumor volume were also obtained. Histopathologic features included tumor grade, Ki-67, mitotic count, necrosis, microvascular proliferation, and molecular alterations (isocitrate dehydrogenase [IDH], 1p/19q, cyclin-dependent kinase inhibitors 2A and 2B [CDKN2A/B], and p53). Regression models predicted tumor grade (low: 1–2, high: 3–4) using ITSS, tumor volume, and rCBV. ROC curves and diagnostic performance metrics were analyzed. Results: 99 patients were included. ITSS grading correlated with rCBV, tumor volume, mitotic count, Ki-67, and tumor grade (p < 0.001). ITSS grades 0–1 were associated with oligodendrogliomas and astrocytomas (p < 0.001), IDH mutations (p < 0.001), and 1p/19q co-deletions (p = 0.01). ITSS grades 2–3 were linked to glioblastomas (p < 0.001), necrosis (p < 0.001), microvascular proliferation (p < 0.001), and CDKN2A/B homozygous deletions (p = 0.02). Models combining ITSS with rCBV and volume showed AUC of 0.94 and 0.96 (p < 0.001), outperforming univariate models. Conclusions: Semiquantitative ITSS grading correlates with key histopathologic and molecular glioma features. Combined with perfusion and volumetric parameters, ITSS enhance non-invasive glioma grading, in alignment with WHO CNS5. Full article

Objectives: To assess amide proton transfer weighted (APTw) MR imaging capabilities in differentiating high-grade glial tumors across alpha-thalassemia/mental retardation X-linked (ATRX) expression, tumor-suppressor protein p53 expression (p53), O6-methylguanine-DNA methyltransferase promoter (MGMTp) methylation, isocitrate dehydrogenase (IDH) status, and proliferation marker Ki-67 (Ki-67 index) as a preoperative diagnostic aid. Material & Methods: A total of 42 high-grade glioma WHO grade 4 (HGG) patients were evaluated prospectively (30 males and 12 females). All patients were examined using conventional MRI, including the following: T1w-MPRAGE pre- and post-contrast administration, conventional T2w and 3D FLAIR, and APTw imaging with a 3T MR scanner. Receiver operating characteristic (ROC) curves were calculated for the APTw% mean, median, and max signal for the different molecular biomarkers. A logistic regression model was constructed for combined mean and median APTw% signals for p53 expression. Results: The whole-tumor max APTw% signal could significantly differentiate MGMTp from non-MGMTp HGG, p = 0.035. A cutoff of 4.28% max APTw% signal yielded AUC (area under the curve) = 0.702, with 70.6% sensitivity and 66.7% specificity. The mean/median APTw% signals differed significantly in p53 normal versus p53-overexpressed HGG s: 1.81%/1.83% vs. 1.15%/1.18%, p = 0.002/0.006, respectively. Cutoffs of 1.25%/1.33% for the mean/median APTw% signals yielded AUCs of 0.786/0.757, sensitivities of 76.9%/76.9%, and specificities of 50%/66.2%, p = 0.002/0.006, respectively. A logistic regression model with a combined mean and median APTw% signal for p53 status yielded an AUC = 0.788 and 76.9% sensitivity and 66.2% specificity. ATRX-, IDH- wild type (wt) vs. mutation (mut), and the level of Ki-67 did not differ significantly, but trends were found: IDH-wt and low Ki-67 showed higher mean/median/max APTw% signals vs. IDH-mut and high Ki-67, respectively. ATRX-wt vs. mutation showed higher mean and median APTw% signals but lower max APTw% signal. Conclusions: APTw imaging can potentially be a useful marker for the stratification of p53 expression and MGMT status in high-grade glioma in the preoperative setting and potentially aid surgical decision-making. Full article

Gliomas, the most common type of primary brain tumor, are a significant cause of morbidity and mortality worldwide. Glioblastoma, a highly malignant subtype, is particularly common, aggressive, and resistant to treatment. The tumor microenvironment (TME) of gliomas, especially glioblastomas, is characterized by a distinct presence of tumor-associated macrophages (TAMs), which densely infiltrate glioblastomas, a hallmark of these tumors. This macrophage population comprises both tissue-resident microglia as well as macrophages derived from the walls of blood vessels and the blood stream. Ionized calcium-binding adapter molecule 1 (Iba1) and CD163 are established cellular markers that enable the identification and functional characterization of these cells within the TME. This review provides an in-depth examination of the roles of Iba1 and CD163 in malignant gliomas, with a focus on TAM activation, migration, and immunomodulatory functions. Additionally, we will discuss how recent advances in AI-enhanced cell identification and visualization techniques have begun to transform the analysis of TAMs, promising unprecedented precision in their characterization and providing new insights into their roles within the TME. Iba1 and CD163 appear to have both unique and shared roles in glioma pathobiology, and both have the potential to be targeted through different molecular and cellular mechanisms. We discuss the therapeutic potential of Iba1 and CD163 based on available preclinical (experimental) and clinical (human tissue-based) evidence. Full article

Nidogen-2 (NID2) is a critical component of the extracellular matrix (ECM), which plays a regulatory role in cell adhesion, migration, differentiation, and survival. Previous studies have shown that NID2 is deregulated in several types of cancer, but its role in glioma is unknown. The present study investigated the prognostic value of NID2 in glioma and its associated molecular pathways and functional roles in malignant progression. The performed analyses included investigating the NID2 expression profile using the Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and tumor tissue microarray. The findings demonstrated that NID2 high expression predicts worse patient survival by both univariable and multivariable analyses. There is a strong correlation between NID2 upregulation and tumor grade. In stably NID2-overexpressed glioma cells, RNA-Seq analysis revealed coactivation of oncogenic functional pathways, including cell proliferation, survival, epithelial–mesenchymal transition, ECM organization, and migration. Overexpression of NID2 in U87MG and T98G cells promoted cell proliferation, migration, and invasion. TUNEL assay showed NID2 overexpression protected cells from apoptosis. Western blotting analysis showed activation of Akt and Bcl-xL in NID2-overexpressed cells. Our results show that NID2 is a promising prognostic marker in glioma. Full article

The aim of this research was to provide a comparative analysis of the major parameters of the blood lipid spectrum found both in the case of brain tumors and in atherosclerosis, as well as to assess the correlation of these indicators with the proliferative activity index Ki-67 in cells. Blood analyses were conducted on samples from 50 patients with brain tumors and 50 patients with cerebral atherosclerosis. Blood plasma from 50 essentially healthy people was used for controls. Significant differences were found in the parameter values between the atherosclerosis sufferers and the control group only for their ratios of neutral lipids to cholesterol. Of the short-chain fatty acids, butyric acid is of greatest interest due to the significant differences of its levels from the control group in the blood of both patients with meningiomas and of those with gliomas. Statistically significant correlation coefficients between the levels of the Ki-67 cell proliferation marker and, in particular, butyric acid were found when compared with the neutral lipids to cholesterol ratios. These identified parameters of the blood plasma lipid spectrum can be used for preoperative diagnostics of brain tumors. However, these ratios cannot be used as preoperative noninvasive predictors of the level of the Ki-67 mitotic index, as no significant differences corresponding to this were found for low-grade or for high-grade anaplasia of brain tumors. Full article

Background/Objectives: Integrating deep learning (DL) into radiomics offers a noninvasive approach to predicting molecular markers in gliomas, a crucial step toward personalized medicine. This study aimed to assess the diagnostic accuracy of DL models in predicting various glioma molecular markers using MRI. Methods: Following PRISMA guidelines, we systematically searched PubMed, Scopus, Ovid, and Web of Science until 27 February 2024 for studies employing DL algorithms to predict gliomas’ molecular markers from MRI sequences. The publications were assessed for the risk of bias, applicability concerns, and quality using the QUADAS-2 tool and the radiomics quality score (RQS). A bivariate random-effects model estimated pooled sensitivity and specificity, accounting for inter-study heterogeneity. Results: Of 728 articles, 43 were qualified for qualitative analysis, and 30 were included in the meta-analysis. In the validation cohorts, MGMT methylation had a pooled sensitivity of 0.74 (95% CI: 0.66–0.80) and a pooled specificity of 0.75 (95% CI: 0.65–0.82), both with significant heterogeneity (p = 0.00, I² = 80.90–84.50%). ATRX and TERT mutations had a pooled sensitivity of 0.79 (95% CI: 0.67–0.87) and 0.81 (95% CI: 0.72–0.87) and a pooled specificity of 0.85 (95% CI: 0.78–0.91) and 0.70 (95% CI: 0.61–0.77), respectively. Meta-regression analyses revealed that significant heterogeneity was influenced by data sources, MRI sequences, feature extraction methods, and validation techniques. Conclusions: While the DL models show promising prediction accuracy for glioma molecular markers, variability in the study settings complicates clinical translation. To bridge this gap, future efforts should focus on harmonizing multi-center MRI datasets, incorporating external validation, and promoting open-source studies and data sharing. Full article

Diffuse intrinsic pontine glioma (DIPG) is a rare but extremely malignant central nervous system tumor primarily affecting children that is almost universally fatal with a devastating prognosis of 8-to-12-month median survival time following diagnosis. Traditionally, DIPG has been diagnosed via MR imaging alone and treated with palliative radiation therapy. While performing surgical biopsies for these patients has been controversial, in recent years, advancements have been made in the safety and efficacy of surgical biopsy techniques, utilizing stereotactic, robotics, and intraoperative cranial nerve monitoring as well as the development of liquid biopsies that identify tumor markers in either cerebrospinal fluid or serum. With more molecular data being collected from these tumors due to more frequent biopsies being performed, multiple treatment modalities including chemotherapy, radiation therapy, immunotherapy, and epigenetic modifying agents continue to be developed. Numerous recent clinical trials have been completed or are currently ongoing that have shown promise in extending survival for patients with DIPG. Focused ultrasound (FUS) has also emerged as an additional promising adjunct invention used to increase the effectiveness of therapeutic agents. In this review, we discuss the current evidence to date for these advancements in the diagnosis and treatment of DIPG. Full article

Background: Renal cell carcinoma is one of the most aggressive urogenital malignancies, with an increasing number of cases worldwide. The majority of cases are diagnosed at an advanced stage, as this form of growth is typically silent. An accurate evaluation of the extent of the disease is crucial for selecting the most appropriate treatment approach. Nuclear medicine imaging is increasingly being applied in oncological diagnostics, prompting ongoing research into renal cell carcinoma markers that could serve as a foundation for theranostic approaches in this disease. Positron emission tomography/computed tomography imaging with prostate-specific membrane antigen (PSMA) ligands has already demonstrated successful utility in diagnosis of other cancers, including prostate cancer and gliomas. Emerging evidence of high sensitivity and specificity in detecting renal cell carcinoma lesions provides a suitable foundation for its application in both the diagnosis and subsequent management of this malignancy. Methods: This systematic review synthesizes the current scientific evidence on the molecular imaging of renal cell carcinoma using PSMA ligands, emphasizing the potential future applications of this imaging marker in theranostic approaches. Results and Conclusions: Based on a systematic review of the literature, it appears that PET/CT with PSMA ligands has the potential to surpass traditional imaging techniques in diagnostic accuracy while also providing valuable prognostic information. Full article

Gliomas are a heterogeneous group of brain tumors, among which the most aggressive subtype is glioblastoma, accounting for 60% of cases in adults. Available systemic treatment options are few and ineffective, so new approaches to therapies for glioblastoma are in high demand. In total, 131 patients with diffuse glioma were studied. Paired tumor–normal samples were sequenced on the Illumina platform; the panel included 812 genes associated with cancer development. Molecular profiles in clinically distinct groups were investigated. In low-grade glioma (LGG) patients (n = 18), the most common mutations were IDH1/2 (78%), ATRX (33%), TP53 (33%), PIK3CA (17%), and co-deletion 1p/19q (22%). In high-grade glioma (HGG) patients (n = 113), more frequently affected genes were CDKN2A/B (33%), TERTp (71%), PTEN (60%), TP53 (27%), and EGFR (40%). The independent predictors of better prognosis were tumor grade and IDH1/2 mutations. In IDH—wildtype glioblastoma patients, a history of other precedent cancer was associated with worse overall survival (OS), while re-operation and bevacizumab therapy increased OS. Also, among genetic alterations, TERTp mutation and PTEN deletion were markers of poor prognosis. Nine patients received molecular targeted therapy, and the results were evaluated. The search for molecular changes associated with tumor growth and progression is important for diagnosis and choice of therapy. Full article

Background: Molecular profiles can predict which patients will respond to current standard treatment and new targeted therapy regimens. Using data from a highly diverse population of approximately three million in Southeast London and Kent, this study aims to evaluate the prevalence of IDH1 mutation and MGMT promoter methylation in the gliomas diagnosed in adult patients and to explore correlations with patients’ demographic and clinicopathological characteristics. Methods: Anonymised data on 749 adult patients diagnosed with a glioma in 2015–2019 at King’s College Hospital were extracted. Univariable and multivariable logistic regressions were used to estimate odds ratios (ORs) for expressing IDH1 mutation and MGMT promoter methylation, based on each patient’s age, sex, ethnicity, histology, tumour location and extent of resection. The Kaplan–Meier method was used to estimate the overall survival functions. Results: A total of 19.5% of cases were IDH1-mutated. Being 39 years and younger (OR 5.48, 95% CI 3.17–9.47), from Asian/Asian British background (OR 3.68, 95% CI 1.05–12.97), having MGMT methylation (OR 15.92, 95% CI 7.30–34.75), an oligodendroglioma diagnosis (OR 7.45, 95% CI 2.90–19.13) and receiving a gross total/total microscopic resection (OR 1.95, 95% CI 1.24–3.08) were each univariately correlated with IDH1 mutation. MGMT methylation association persisted on adjustment (OR 14.13, 95% CI 3.88–51.43). MGMT promoter methylation was seen in 54.3% of gliomas. In the univariate adjusted ORs, being younger than 39 years (OR 2.56, 95% CI 1.48–4.43), female (OR 1.52, 95% CI 1.11–2.08), having IDH1 mutation (OR 15.92, 95% CI 7.30–34.75) and an oligodendroglioma diagnosis (OR 6.20, 95% CI 1.33–28.88) were associated with MGMT methylation. Being female (OR 1.75, 95% CI 1.22–2.51) and having an IDH1 mutation (OR 15.54, 95% CI 4.73–51.05) persisted after adjustment for age, sex, ethnicity, histology, tumour location and extent of resection. IDH1 mutant and MGMT methylated gliomas were associated with frontal lobe location. Survival analysis showed that patients with both IDH1 mutation and MGMT methylation had significantly better survival than those with either molecular marker alone. Over a 3-year period, women with unmethylated MGMT promoters generally had better survival than men with unmethylated MGMT. Conclusion: This study showed that the molecular markers of IDH1 mutation and MGMT promoter methylation were associated with age, sex, Asian/Asian British ethnic group, tumour histology, anatomical location and extent of resection. This study has demonstrated the importance of assessing glioma molecular markers in the clinical setting and the need to stratify patients according to their clinicopathological characteristics. Full article

DEHP is a plasticizer that is widely found in our water environment and poses a significant risk to the environment and human health. Long-term exposure to DEHP can cause endocrine disruption and interfere with the organism’s normal functioning. In order to explore the potential effects of DEHP on the development of biological brain tissues, this study used bioinformatics analysis to confirm the diagnostic and prognostic value of PER3 in gliomas and further validated the neurotoxicity of DEHP using methods such as behavioral experiments and molecular biology in zebrafish. The experimental findings revealed that the expression level of PER3 in diseased tissues was significantly lower than that in the control group. In addition, the expression level of PER3 was significantly correlated with immune cell infiltration, immune checkpoint genes, and oncogenes. Moreover, the ROC curve analysis showed that PER3 could accurately differentiate between GBM tissues and adjacent normal tissues. To further validate the neurotoxicity of DEHP, we analyzed the effects of DEHP exposure on zebrafish development and PER3 expression by behavioral experiments and molecular biology. The results showed that exposure to DEHP substantially altered both the behavioral responses and the gene expression profiles within the brain tissues of zebrafish. PCR results indicate that the expression of circadian rhythm factor PER3 was significantly reduced in the brains of zebrafish in the exposed group, and circadian dysregulation had a certain promoting effect on the development of glioma. The aim of this work was to investigate the potential effects of DEHP contamination in a water environment on organism brain development. It was demonstrated that PER3 is an effective early diagnostic marker, which is of great significance in the diagnosis and clinical prognosis of glioma, and that DEHP exposure can lead to a significant reduction in PER3 expression in zebrafish brain tissue. This study further proved that DEHP has a potential carcinogenic effect, which adds scientific evidence to the carcinogenicity study of DEHP. Full article

Isocitrate dehydrogenase (IDH) and O⁶-methylguanine-DNA methyltransferase (MGMT) genes are critical molecular markers in determining treatment options and predicting the prognosis of adult-type diffuse gliomas. Objectives: this study aimed to investigate whether multimodal MRI enables the differentiation of genotypes in adult-type diffuse gliomas. Methods: a total of 116 adult-type diffuse glioma patients (61 males, 51.5 (37, 62) years old) who underwent multimodal MRI before surgery were retrospectively analysed. Multimodal MRI included conventional MRI, proton magnetic resonance spectroscopy (¹H-MRS), and diffusion tensor imaging (DTI). Conventional visual features, N-acetyl-aspartate (NAA)/Creatine (Cr), Choline (Cho)/Cr, Cho/NAA, fractional anisotropy (FA), mean diffusivity (MD), and diffusion histogram parameters were extracted on the whole tumour. Multimodal MRI parameters of IDH-mutant and IDH-wildtype gliomas were compared using the Mann–Whitney U test, Student’s t-test, or Pearson chi-square tests. Logistic regression was used to select the MRI parameters to predict IDH-mutant gliomas. Furthermore, multimodal MRI parameters were selected to establish models for predicting MGMT methylation in the IDH-wildtype gliomas. The performance of models was evaluated by the receiver operating characteristics curve. Results: a total of 56 patients with IDH-mutant gliomas and 60 patients with IDH-wildtype glioblastomas (GBM) (37 with methylated MGMT and 17 with unmethylated MGMT) were diagnosed by 2021 WHO classification criteria. The enhancement degree (OR = 4.298, p < 0.001), necrosis/cyst (OR = 5.381, p = 0.011), NAA/Cr (OR = 0.497, p = 0.037), FA-Skewness (OR = 0.497, p = 0.033), MD-Skewness (OR = 1.849, p = 0.035), FA_mean (OR = 1.924, p = 0.049) were independent factors for the multimodal combined prediction model in predicting IDH-mutant gliomas. The combined modal based on conventional MRI, ¹H-MRS, DTI parameters, and histogram performed best in predicting IDH-wildtype status (AUC = 0.890). However, only NAA/Cr (OR = 0.17, p = 0.043) and FA (OR = 0.38, p = 0.015) were associated with MGMT methylated in IDH-wildtype GBM. The combination of NAA/Cr and FA-Median is more accurate for predicting MGMT methylation levels than using these elements alone (AUC, 0.847 vs. 0.695/0.684). Conclusions: multimodal MRI based on conventional MRI, ¹H-MRS, and DTI can provide compound imaging markers for stratified individual diagnosis of IDH mutant and MGMT promoter methylation in adult-type diffuse gliomas. Full article

Central nervous system (CNS) tumors represent a formidable clinical challenge due to their molecular complexity and varied prognostic outcomes. This review delves into the pivotal role of the epigenetic marker H3K27me3 in the development and treatment of CNS tumors. H3K27me3, specifically the trimethylation of lysine 27 on the histone H3 protein, plays a crucial role in regulating gene expression and maintaining chromatin architecture (e.g., in X-chromosome inactivation). Notably, a reduction in H3K27me3 levels, frequently tied to mutations in the H3 gene family such as H3F3A and HIST1H3B, is evident in diverse brain tumor variants, including the diffuse midline glioma characterized by the H3K27M mutation and certain pediatric high-grade gliomas. The loss of H3K27me3 has been linked to more aggressive behavior in meningiomas, with the trimethylation loss associated with significantly shorter recurrence-free survival (RFS) among grade 2 meningiomas, albeit not within grade 1 tumors. Pediatric posterior fossa ependymomas characterized by a lowered H3K27me3 and DNA hypomethylation exhibit poor prognosis, underscoring the prognostic significance of these epigenetic alterations in CNS tumors. Comprehending the role of H3K27me3 in CNS tumors is vital for advancing diagnostic tools and therapeutic interventions, with the goal of enhancing patient outcomes and quality of life. This review underscores the importance of ongoing investigations into H3K27me to refine and optimize management strategies for CNS tumors, paving the way for improved personalized medicine practices in oncology. Full article

This case report delves into the case of a 56-year-old female patient presenting with progressive cephalalgia syndrome, nausea, vomiting, and gait disorders, diagnosed with a high-grade thalamic glioma. Glioma is the most common form of central nervous system (CNS) neoplasm that originates from glial cells. Gliomas are diffusely infiltrative tumors that affect the surrounding brain tissue. Glioblastoma is the most malignant type, while pilocytic astrocytomas are the least malignant brain tumors. In the past, these diffuse gliomas were classified into different subtypes and grades based on histopathologies such as a diffuse astrocytoma, oligodendrogliomas, or mixed gliomas/oligoastrocytomas. Currently, gliomas are classified based on molecular and genetic markers. After the gross total resection, a postoperative brain CT scan was conducted, which confirmed the quasi-complete resection of the tumor. The successful gross total resection of the tumor in this case, coupled with significant neurological improvement postoperatively, illustrates the potential benefits of aggressive surgical management for thalamic gliomas. This report advocates for further research to assess the efficacy of such interventions in malignant cases and to establish standardized treatment protocols, considering the heterogeneity in prognostic outcomes and the advancements in molecular diagnostics that offer deeper insights into glioma oncogenesis and progression. Full article