-
Redox Biology Jun 2024The oncogene Aurora kinase A (AURKA) has been implicated in various tumor, yet its role in meningioma remains unexplored. Recent studies have suggested a potential link...
The oncogene Aurora kinase A (AURKA) has been implicated in various tumor, yet its role in meningioma remains unexplored. Recent studies have suggested a potential link between AURKA and ferroptosis, although the underlying mechanisms are unclear. This study presented evidence of AURKA upregulation in high grade meningioma and its ability to enhance malignant characteristics. We identified AURKA as a suppressor of erastin-induced ferroptosis in meningioma. Mechanistically, AURKA directly interacted with and phosphorylated kelch-like ECH-associated protein 1 (KEAP1), thereby activating nuclear factor erythroid 2 related factor 2 (NFE2L2/NRF2) and target genes transcription. Additionally, forkhead box protein M1 (FOXM1) facilitated the transcription of AURKA. Suppression of AURKA, in conjunction with erastin, yields significant enhancements in the prognosis of a murine model of meningioma. Our study elucidates an unidentified mechanism by which AURKA governs ferroptosis, and strongly suggests that the combination of AURKA inhibition and ferroptosis-inducing agents could potentially provide therapeutic benefits for meningioma treatment.
Topics: Ferroptosis; Forkhead Box Protein M1; Aurora Kinase A; Humans; NF-E2-Related Factor 2; Animals; Mice; Meningioma; Piperazines; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Signal Transduction; Kelch-Like ECH-Associated Protein 1; Meningeal Neoplasms; Drug Resistance, Neoplasm
PubMed: 38642502
DOI: 10.1016/j.redox.2024.103137 -
Nature Communications Oct 2023Hedgehog signaling mediates embryologic development of the central nervous system and other tissues and is frequently hijacked by neoplasia to facilitate uncontrolled...
Hedgehog signaling mediates embryologic development of the central nervous system and other tissues and is frequently hijacked by neoplasia to facilitate uncontrolled cellular proliferation. Meningiomas, the most common primary brain tumor, exhibit Hedgehog signaling activation in 6.5% of cases, triggered by recurrent mutations in pathway mediators such as SMO. In this study, we find 35.6% of meningiomas that lack previously known drivers acquired various types of somatic structural variations affecting chromosomes 2q35 and 7q36.3. These cases exhibit ectopic expression of Hedgehog ligands, IHH and SHH, respectively, resulting in Hedgehog signaling activation. Recurrent tandem duplications involving IHH permit de novo chromatin interactions between super-enhancers within DIRC3 and a locus containing IHH. Our work expands the landscape of meningioma molecular drivers and demonstrates enhancer hijacking of Hedgehog ligands as a route to activate this pathway in neoplasia.
Topics: Humans; Hedgehog Proteins; Meningioma; Ligands; Signal Transduction; Meningeal Neoplasms
PubMed: 37805627
DOI: 10.1038/s41467-023-41926-y -
Surgical Neurology International 2024Meningioma, the most common brain tumor, traditionally considered benign, has a relatively high risk of recurrence over a patient's lifespan. In addition, with the... (Review)
Review
BACKGROUND
Meningioma, the most common brain tumor, traditionally considered benign, has a relatively high risk of recurrence over a patient's lifespan. In addition, with the emergence of several clinical, radiological, and molecular variables, it is becoming evident that existing grading criteria, including Simpson's and World Health Organization classification, may not be sufficient or accurate. As web-based tools for widespread accessibility and usage become commonplace, such as those for gene identification or other cancers, it is timely for meningioma care to take advantage of evolving new markers to help advance patient care.
METHODS
A scoping review of the meningioma literature was undertaken using the MEDLINE and Embase databases. We reviewed original studies and review articles from September 2022 to December 2023 that provided the most updated information on the demographic, clinical, radiographic, histopathological, molecular genetics, and management of meningiomas in the adult population.
RESULTS
Our scoping review reveals a large body of meningioma literature that has evaluated the determinants for recurrence and aggressive tumor biology, including older age, female sex, genetic abnormalities such as telomerase reverse transcriptase promoter mutation, deletion, subtotal resection, and higher grade. Despite a large body of evidence on meningiomas, however, we noted a lack of tools to aid the clinician in decision-making. We identified the need for an online, self-updating, and machine-learning-based dynamic model that can incorporate demographic, clinical, radiographic, histopathological, and genetic variables to predict the recurrence risk of meningiomas.
CONCLUSION
Although a challenging endeavor, a recurrence prediction tool for meningioma would provide critical information for the meningioma patient and the clinician making decisions on long-term surveillance and management of meningiomas.
PubMed: 38840600
DOI: 10.25259/SNI_43_2024 -
Cancers Jul 2023This series of five articles (one original article and four reviews) focuses on the most recent and interesting research studies on the biomolecular and radiological...
This series of five articles (one original article and four reviews) focuses on the most recent and interesting research studies on the biomolecular and radiological diagnosis and the surgical and medical management of meningiomas [...].
PubMed: 37509238
DOI: 10.3390/cancers15143575 -
The Kaohsiung Journal of Medical... Nov 2023
Topics: Humans; Meningioma; Lung Neoplasms; Tomography, X-Ray Computed; Meningeal Neoplasms
PubMed: 37698283
DOI: 10.1002/kjm2.12754 -
PloS One 2024Meningioma is the most common primary brain tumor and many studies have evaluated numerous biomarkers for their prognostic value, often with inconsistent results.... (Meta-Analysis)
Meta-Analysis
Meningioma is the most common primary brain tumor and many studies have evaluated numerous biomarkers for their prognostic value, often with inconsistent results. Currently, no reliable biomarkers are available to predict the survival, recurrence, and progression of meningioma patients in clinical practice. This study aims to evaluate the prognostic value of immunohistochemistry-based (IHC) biomarkers of meningioma patients. A systematic literature search was conducted up to November 2023 on PubMed, CENTRAL, CINAHL Plus, and Scopus databases. Two authors independently reviewed the identified relevant studies, extracted data, and assessed the risk of bias of the studies included. Meta-analyses were performed with the hazard ratio (HR) and 95% confidence interval (CI) of overall survival (OS), recurrence-free survival (RFS), and progression-free survival (PFS). The risk of bias in the included studies was evaluated using the Quality in Prognosis Studies (QUIPS) tool. A total of 100 studies with 16,745 patients were included in this review. As the promising markers to predict OS of meningioma patients, Ki-67/MIB-1 (HR = 1.03, 95%CI 1.02 to 1.05) was identified to associate with poor prognosis of the patients. Overexpression of cyclin A (HR = 4.91, 95%CI 1.38 to 17.44), topoisomerase II α (TOP2A) (HR = 4.90, 95%CI 2.96 to 8.12), p53 (HR = 2.40, 95%CI 1.73 to 3.34), vascular endothelial growth factor (VEGF) (HR = 1.61, 95%CI 1.36 to 1.90), and Ki-67 (HR = 1.33, 95%CI 1.21 to 1.46), were identified also as unfavorable prognostic biomarkers for poor RFS of meningioma patients. Conversely, positive progesterone receptor (PR) and p21 staining were associated with longer RFS and are considered biomarkers of favorable prognosis of meningioma patients (HR = 0.60, 95% CI 0.41 to 0.88 and HR = 1.89, 95%CI 1.11 to 3.20). Additionally, high expression of Ki-67 was identified as a prognosis biomarker for poor PFS of meningioma patients (HR = 1.02, 95%CI 1.00 to 1.04). Although only in single studies, KPNA2, CDK6, Cox-2, MCM7 and PCNA are proposed as additional markers with high expression that are related with poor prognosis of meningioma patients. In conclusion, the results of the meta-analysis demonstrated that PR, cyclin A, TOP2A, p21, p53, VEGF and Ki-67 are either positively or negatively associated with survival of meningioma patients and might be useful biomarkers to assess the prognosis.
Topics: Meningioma; Humans; Biomarkers, Tumor; Prognosis; Meningeal Neoplasms; DNA Topoisomerases, Type II; Ki-67 Antigen; Tumor Suppressor Protein p53; Vascular Endothelial Growth Factor A; Immunohistochemistry; Poly-ADP-Ribose Binding Proteins
PubMed: 38758750
DOI: 10.1371/journal.pone.0303337 -
Acta Neurochirurgica Oct 2023Meningiomas are the most common primary intracranial tumor. While the majority of meningiomas are benign, rarely they can metastasize extracranially. There is a need for...
BACKGROUND
Meningiomas are the most common primary intracranial tumor. While the majority of meningiomas are benign, rarely they can metastasize extracranially. There is a need for a more comprehensive review of these patients to improve our understanding of this rare phenomenon and its prevalence globally. Here we describe our institution's experience of patients presenting with metastatic meningiomas. We further perform a systematic review of the existing literature to explore common features of this rare manifestation of meningioma and review the efficacy of current treatments.
METHODS
We performed a retrospective clinical review of all adult patients with metastatic meningioma managed at our institution over the past 20 years, identifying 6 patients. We then performed a systematic review of cases of metastatic meningioma in the literature ranging from the years 1886 to 2022. A descriptive analysis was then conducted on the available data from 1979 onward, focusing on the grade and location of the primary tumor as well as the latency period to, and location of, the metastasis.
RESULTS
In total, we analyzed 155 cases. Fifty-four percent of patients initially presented with a primary meningioma located in the convexity. The most common site of metastasis was the lung. Risk factors associated with a shorter time to metastasis were male sex and a high initial grade of the tumor. Regarding treatment, the addition of chemotherapy was the most common adjunct to the standard management of surgery and radiotherapy. Despite an exhaustive review we were unable to identify effective treatments. The majority of published cases came from centers situated in high-income countries (84%) while only 16% came from lower- and middle-income countries.
CONCLUSIONS
Metastatic meningiomas pose a pertinent, and likely underestimated, clinical challenge within modern neurosurgery. To optimize management, timely identification of these patients is important. More research is needed to explore the mechanisms underlying these tumors to better guide the development of effective screening and management protocols. However, screening of each meningioma patient is not feasible, and at the heart of this challenge is the inability to control the primary disease. Ultimately, a consensus is needed as to how to correctly screen for and manage these patients; genomic and epigenomic approaches could hold the answer to finding druggable targets.
Topics: Adult; Female; Humans; Male; Brain Neoplasms; Meningeal Neoplasms; Meningioma; Retrospective Studies; Treatment Outcome
PubMed: 37491650
DOI: 10.1007/s00701-023-05687-3 -
Frontiers in Neurology 2023Headache during pregnancy can be due to primary causes such as migraine but can also be a presenting symptom of secondary causes including life threatening conditions.... (Review)
Review
Headache during pregnancy can be due to primary causes such as migraine but can also be a presenting symptom of secondary causes including life threatening conditions. This is a minireview of secondary causes of headache during pregnancy and the puerperium. Unique alterations in physiological and vascular functions as well as in the coagulation pathway which occur during pregnancy increase the risk of most of these secondary conditions which include preeclampsia, eclampsia, hemorrhagic stroke, cerebral venous, sinus thrombosis, reversible cerebral vascular syndrome, and posterior reversible encephalopathy. Marked increase in progesterone level in pregnancy is also associated with the growth of tumors such as meningiomas, as 70% of these tumors are positive for progesterone receptors and increase in size can lead to headache along with other neurological symptoms. Hemodynamic changes can lead to the growth of meningiomas as well. Although hormone producing pituitary tumors are usually not conducing to pregnancy, women with known pituitary tumors who do get pregnant may become symptomatic during pregnancy and develop secondary headache. Another rare cause of secondary headache during pregnancy is pituitary apoplexy. Although its occurrence is uncommon, it needs to be properly recognized and treated to avoid endocrine and visual complications. Other rare entities with increased incidence during the puerperium such postdural puncture headache will be also discussed. In summary, new onset headache during pregnancy deserves special attention because in the absence of proper recognition and treatment, secondary headache disorders can endanger the life of the mother and the fetus.
PubMed: 37840942
DOI: 10.3389/fneur.2023.1239078 -
Frontiers in Neurology 2023Studies have shown that longer leukocyte telomere length (LTL) is significantly associated with increased risk of meningioma. However, there is limited evidence...
BACKGROUND
Studies have shown that longer leukocyte telomere length (LTL) is significantly associated with increased risk of meningioma. However, there is limited evidence concerning the causal association of LTL with benign and malignant meningiomas or with the location of benign tumors.
METHODS
We used three LTL datasets from different sources, designated by name and sample size as LTL-78592, LTL-9190, and LTL-472174. The linkage disequilibrium score (LDSC) was used to explore the association between LTL and meningioma. We utilized two-sample bidirectional Mendelian randomization (TSMR) to evaluate whether LTL is causally related to meningioma risk. We adjusted for confounders by conducting multivariable Mendelian randomization (MVMR).
RESULTS
In the LTL-78592, longer LTL was significantly associated with increased risk of malignant [odds ratio (OR) = 5.14, = 1.04 × 10], benign (OR = 4.81, < 0.05), benign cerebral (OR = 5.36, < 0.05), and benign unspecified meningioma (OR = 8.26, < 0.05). The same results were obtained for the LTL-9190. In the LTL-472174, longer LTL was significantly associated with increased risk of malignant (OR = 4.94, < 0.05), benign (OR = 3.14, < 0.05), and benign cerebral meningioma (OR = 3.59, < 0.05). Similar results were obtained in the MVMR. In contrast, only benign cerebral meningioma displayed a possible association with longer LTL (OR = 1.01, < 0.05). No heterogeneity or horizontal pleiotropy was detected.
CONCLUSION
In brief, genetically predicted longer LTL may increase the risk of benign, malignant, and benign cerebral meningiomas, regardless of the LTL measure, in European populations.
PubMed: 37693759
DOI: 10.3389/fneur.2023.1178404 -
Acta Neuropathologica Aug 2023Meningiomas are the most common primary intracranial tumors. Although most symptomatic cases can be managed by surgery and/or radiotherapy, a relevant number of patients...
Meningiomas are the most common primary intracranial tumors. Although most symptomatic cases can be managed by surgery and/or radiotherapy, a relevant number of patients experience an unfavorable clinical course and additional treatment options are needed. As meningiomas are often perfused by dural branches of the external carotid artery, which is located outside the blood-brain barrier, they might be an accessible target for immunotherapy. However, the landscape of naturally presented tumor antigens in meningioma is unknown. We here provide a T-cell antigen atlas for meningioma by in-depth profiling of the naturally presented immunopeptidome using LC-MS/MS. Candidate target antigens were selected based on a comparative approach using an extensive immunopeptidome data set of normal tissues. Meningioma-exclusive antigens for HLA class I and II are described here for the first time. Top-ranking targets were further functionally characterized by showing their immunogenicity through in vitro T-cell priming assays. Thus, we provide an atlas of meningioma T-cell antigens which will be publicly available for further research. In addition, we have identified novel actionable targets that warrant further investigation as an immunotherapy option for meningioma.
Topics: Humans; Meningioma; Chromatography, Liquid; Tandem Mass Spectrometry; Immunotherapy; T-Lymphocytes; Meningeal Neoplasms
PubMed: 37368072
DOI: 10.1007/s00401-023-02605-w