Prediction of Meningioma Grade Using Hematological Parameters.

OBJECTIVE: Predicting the aggressiveness of meningiomas may influence the surgical strategy timing. Because of the paucity of robust markers, the systemic immune-inflammation (SII) index is a novel biomarker to be an independent predictor of poor prognosis in various cancers including gliomas. We aimed to investigate the value of SII as well as neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) indices in predicting prognosis. METHODS: Records including demographic, clinical, and laboratory data of patients operated on due to intracranial meningioma in 2017-2023 were retrospectively reviewed. RESULTS: A total of 234 patients were included in this study. All of SII index, NLR, and PLR values at presentation were significantly higher in grade ≥2 meningiomas. A positive correlation was observed between SII index and Ki67 index (r=0.313; P<0.001); between NLR and Ki67 index (r=0.330; P<0.001); and between PLR and Ki67 index (r=0.223; P<0.01). SII index (optimal cutoff level >618), NLR (optimal cutoff level >3.53), and PLR (optimal cutoff level >121.2) showed significant predictive values. CONCLUSIONS: This is the first study to assess the prognostic value of the SII index in patients with intracranial meningiomas. Increased SII index, NLR and PLR were correlated with higher grade and higher Ki-67 index. They also harbor the potential to screen patients that may need more aggressive treatments or more frequent follow-up examinations.

A randomized control trial for evaluation of transfusion related immuno-modulation in patients with meningioma.

BACKGROUND: Blood transfusion necessity in neurosurgery varies based on surgical type, blood loss, and patient anemia. Leukocytes in red blood cells (RBCs) component release pro-inflammatory cytokines during storage, contributing to transfusion-related immunomodulation (TRIM). Our aim was to examine the impact of the leukocyte content in transfused PRBCs on patients undergoing neurosurgery for meningioma tumours. STUDY DESIGN AND METHODS: This prospective randomized controlled trial conducted from 2018 to 2020 by dividing patients randomly into non-leukoreduced (NLR) (n = 65) and leuko-reduced (LR) (n = 65) groups based on PRBCs received during surgery and hospital stay. Hospital and ICU stays, mechanical ventilation duration, and postoperative bacterial infections were observed. Hematological parameters and cytokine levels (IL-10, INF-gamma, and FAS-L) were assessed at pre-transfusion, 24 h, and 7 days post-transfusion. Data analysis included Mann-Whitney U test, Friedman test, Fisher's chi-square test, with statistical significance at p < 0.05. RESULTS: In our study, ICU and hospital stay duration showed no significant difference (p = 0.06) between groups. However, NLR group had longer mean mechanical ventilation (18 ± 40.1 h) than the LR group (12.8 ± 8.6 h). Both groups showed statistically significant increase in Fas-L level on days 1 and 7 (p < 0.05). The IL-10 levels rose 43% in the NLR group, while and decreased by 7% the LR group on day 1. On day 7, IL-10 increased by 75% in NLR and decreased by 40% in LR, with no significance (p > 0.05). CONCLUSION: In conclusion, leukoreduction appeared to offer some immune response protection in term of reducing mechanical ventilation timings and cytokine level changes.

Systemic coagulation is activated in patients with meningioma and glioblastoma.

PURPOSE: Up to 30% of patients with glioblastoma (GBM) develop venous thromboembolism (VTE) over the course of the disease. Although not as high, the risk for VTE is also increased in patients with meningioma. Direct measurement of peak thrombin generation (TG) allows quantitative assessment of systemic coagulation activation in patients with GBM and meningioma. Our aim was to determine the extent of systemic coagulation activation induced by brain tumors, to measure the shift between pre- and post-operative peak TG in patients with GBM, and to assess the relationship between pre-surgical peak TG and pre-operative brain tumor volume on imaging. METHODS: Pre- and post-surgical plasma samples were obtained from successive patients with GBM and once from patients with meningioma and healthy age- and sex-matched blood donor controls. TG was measured using the calibrated automated thrombogram (CAT) assay, and tumor volumes were measured in pre-surgical MRI scans. RESULTS: Pre-surgical peak TG was higher in patients with GBM than in controls (288.6 ± 54.1 nM vs 187.1 ± 41.7 nM, respectively, P < 0.001), and, in the nine patients with GBM and paired data available, peak TG was significantly reduced after surgery (323 ± 38 nM vs 265 ± 52 nM, respectively, P = 0.007). Similarly, subjects with meningioma demonstrated higher peak TG compared to controls (242.2 ± 54.9 nM vs 177.7 ± 57.0 nM, respectively, P < 0.001). There was no association between peak TG and pre-operative tumor volume or overall survival. CONCLUSION: Our results indicate that systemic coagulation activation occurs with both meningioma and GBM, but to a greater degree in the latter. Preoperative peak TG did not correlate with tumor volume, but removal of GBM caused a significant decrease in coagulation activation.

Circulating Levels of Thrombospondin-1 and Thrombospondin-2 in Patients with Common Brain Tumors.

AIM: To measure serum levels of thrombospondin-1 (TSP-1) and thrombospondin-2 (TSP-2) in patients with common brain tumors, namely high-grade glioma (HGG), low-grade glioma (LGG), and meningioma. MATERIAL AND METHODS: For this prospective study, a total of 56 patients were operated on for supratentorial gliomas and meningiomas, and 18 healthy subjects were evaluated. Serum levels of angiostatic molecules were measured with enzyme-linked immunosorbent assay. The results of patients were compared with those of healthy subjects. RESULTS: High serum levels of TSP-1 were seen in HGG, followed by LGG, meningioma groups, and controls. The only significant difference was found between HGGs and controls (p=0.004). There was a trend to decrease from HGG to controls. High serum levels of TSP-2 were seen in controls, followed by meningioma, LGG, and HGG. None of the patient groups showed significant differences compared with controls. Among the patient groups, TSP-2 was significantly higher in the meningioma group than the HGG group (p=0.01). No correlation was found with any of the molecules and the clinical parameters, including the presence of peritumoral edema or seizure, the anterior-posterior diameter of the tumor, and, more importantly, the grade of glioma. CONCLUSION: Our results indicate that TSP-2 might be more important than TSP-1 in preventing angiogenesis and a major angiostatic factor in glioma cells.

Fibulin-2: A Novel Biomarker for Differentiating Grade II from Grade I Meningiomas.

There is an unmet need for the identification of biomarkers to aid in the diagnosis, clinical management, prognosis and follow-up of meningiomas. There is currently no consensus on the optimum management of WHO grade II meningiomas. In this study, we identified the calcium binding extracellular matrix glycoprotein, Fibulin-2, via mass-spectrometry-based proteomics, assessed its expression in grade I and II meningiomas and explored its potential as a grade II biomarker. A total of 87 grade I and 91 grade II different meningioma cells, tissue and plasma samples were used for the various experimental techniques employed to assess Fibulin-2 expression. The tumours were reviewed and classified according to the 2016 edition of the Classification of the Tumours of the central nervous system (CNS). Mass spectrometry proteomic analysis identified Fibulin-2 as a differentially expressed protein between grade I and II meningioma cell cultures. Fibulin-2 levels were further evaluated in meningioma cells using Western blotting and Real-time Quantitative Polymerase Chain Reaction (RT-qPCR); in meningioma tissues via immunohistochemistry and RT-qPCR; and in plasma via Enzyme-Linked Immunosorbent Assay (ELISA). Proteomic analyses (p < 0.05), Western blotting (p < 0.05) and RT-qPCR (p < 0.01) confirmed significantly higher Fibulin-2 (FBLN2) expression levels in grade II meningiomas compared to grade I. Fibulin-2 blood plasma levels were also significantly higher in grade II meningioma patients compared to grade I patients. This study suggests that elevated Fibulin-2 might be a novel grade II meningioma biomarker, when differentiating them from the grade I tumours. The trend of Fibulin-2 expression observed in plasma may serve as a useful non-invasive biomarker.

Somatic mitochondrial DNA D-loop mutations in meningioma discovered: A preliminary data.

BACKGROUND AND OBJECTIVE: Meningiomas are among the most common intracranial tumors of the central nervous system. It is widely accepted that the initiation and progression of meningiomas involve the accumulation of nucleus genetic alterations, but little is known about the implication of mitochondrial genomic alterations during development of these tumors. The human mitochondrial DNA (mtDNA) contains a short hypervariable, noncoding displacement loop control region known as the D-Loop. Alterations in the mtDNA D-loop have been reported to occur in most types of human cancers. The purpose of this study was to assess the mtDNA D-loop mutations in Malaysian meningioma patients. MATERIALS AND METHODS: Genomic DNA was extracted from 21 fresh-frozen tumor tissues and blood samples of the same meningioma patients. The entire mtDNA D-loop region (positions 16024-576) was polymerase chain reaction amplified using designed primers, and then amplification products were purified before the direct DNA sequencing proceeds. RESULTS: Overall, 10 (47.6%) patients were detected to harbor a total of 27 somatic mtDNA D-loop mutations. Most of these mtDNA mutations were identified in the hypervariable segment II (40.7%), with 33.3% being located mainly in the conserved sequence block II of the D310 sequence. Furthermore, 58 different germline variations were observed at 21 nucleotide positions. CONCLUSION: Our results suggest that mtDNA alterations in the D-loop region may be an important and early event in developing meningioma. Further studies are needed, including validation in a larger patient cohort, to verify the clinicopathological outcomes of mtDNA mutation biomarkers in meningiomas.

Total DNA methylation as a biomarker of DNA damage and tumor malignancy in intracranial meningiomas.

BACKGROUND: Meningiomas are the most common primary intracranial tumors in adults. They are initially detected with neuroimaging techniques, but definite histological diagnosis requires tumor surgery to collect tumor tissue. Gross total resection is an optimal and final treatment for the majority of patients, followed by radiotherapy in malignant or refractory cases. However, there are a lot of uncertainties about i.a. the need for intervention in incidental cases, estimation of growth kinetics, risk of malignant transformation, or response to radiotherapy. Therefore a new diagnostic approach is needed. It has already been shown that epigenetics plays a crucial role in cancer biology, development, and progression. DNA methylation, the presence of 5-methylcytosine in DNA, is one of the main elements of a broad epigenetic program in a eukaryotic cell, with superior regulatory significance. Therefore, we decided to look at meningioma through changes of 5-methylcytosine. METHODS: We performed an analysis of the total amount of 5-methylcytosine in DNA isolated from intracranial meningioma tissues and peripheral blood samples of the same patients. The separation and identification of radioactively labeled nucleotides were performed using thin-layer chromatography. RESULTS: We found that the 5-methylcytosine level in DNA from intracranial meningiomas is inversely proportional to the malignancy grade. The higher the tumor WHO grade is, the lower the total DNA methylation. The amount of 5-methylcytosine in tumor tissue and peripheral blood is almost identical. CONCLUSIONS: We conclude that the total DNA methylation can be a useful marker for brain meningioma detection, differentiation, and monitoring. It correlates with tumor WHO grade, and the 5-methylcytosine level in peripheral blood reflects that in tumor tissue. Therefore it's applicable for liquid biopsy. Our study creates a scope for further research on epigenetic mechanisms in neurooncology and can lead to the development of new diagnostic methods in clinical practice.

Evaluation of VEGF, FGF and PDGF and Serum Levels of Inflammatory Cytokines in Patients with Glioma and Meningioma in Southern Iran.

BACKGROUND: Meningioma and glioma are common central nervous system tumors. Hypoxic tumor cells secrete angiogenic cytokines, such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) that stimulate neovascular formation and inflammatory cytokine, such as TNF-α and IL-1ß. We measured these serum levels in patients with glial cell tumors and meningioma. MATERIALS AND METHODS: This was a case-control study in 2014-2015 on patients diagnosed with meningioma/glioma. All demographic and clinical data were registered. The tumor volume and intraoperative bleeding were recorded. Serum levels of VEGF, PDGF, FGF, TNF-α and IL-1ß were measured by ELISA methods. RESULTS: Ninety-six patients were enrolled in this study, 32 in each group. Patients VEGF level with cranial tumor, glioma/meningioma had increased. VEGF level was highest among grade IV tumors, larger tumors, and in glioblastoma multiform. There was an upsurge in VEGF serum level as glioma grade increased. The highest VEGF levels were seen in parasagittal meningioma. In contrast to VEGF, PDGF was slightly elevated in glial cell tumors, which was significantly elevated in meningioma. Higher PDGF correlated with increased intraoperative bleeding, especially in meningioma cases. Oligodendroglial tumors expressed higher PDGF levels in contrast to other glial tumors. FGF level was not statistically significant. TNF-α and IL-1ß expressions were significantly higher in the meningioma and glioma group in comparison to control group. CONCLUSION: We found increased VEGF and PDGF serum levels in CNS patient's tumor. A different role for PDGF was found in the pathogenesis of neovascularization of meningioma, as well as oligodendroglioma. No significant result was found for FGF. TNF-α and IL-1ß can serve as key prognostic biomarker in high-grade glioma and meningioma patients.

Common genetic variations of deiodinase genes and prognosis of brain tumor patients.

BACKGROUND: Thyroid hormone (TH) metabolism can have prognostic significance in brain tumors. We studied the association of common variations in three deiodinase gene single-nucleotide polymorphisms (SNPs) with circulating TH concentrations and prognosis of brain tumor patients. METHODS: Patients admitted for glioma and meningioma surgery between January, 2010 and September, 2011 were evaluated for functional status (Barthel Index or BI) and circulating free tri-iodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) concentrations. Ten common SNPs in the DIO1 gene; five SNPs in the DIO2 gene; and one SNP in the DIO3 gene were genotyped. Follow-up continued until November, 2017. RESULTS: In glioblastoma patients, the DIO1 SNP rs2235544 CC genotype was associated with significantly lower risk of death at 2 years when compared to AA + CA genotypes after adjusting for patient gender, age, pre-operative functional status, adjuvant therapy, and extent of resection (HR = 0.34, 95% CI: 0.13-0.84, p = 0.019). The TT genotype vs. CC + TC genotypes of the DI02 SNP rs12885300 was associated with increased mortality risk after adjusting for patient gender, age, pre-operative functional status, adjuvant therapy, extent of resection, and FT3/FT4 (HR = 3.13, 95% CI: 1.20-8.16, p < 0.019). The C-allele of the DI01 SNP rs2235544 was related to increased circulating free T3/ free T4 ratio in glioma and meningioma patients, indicating greater T4 to T3 conversion. CONCLUSIONS: SNPs of DIO1 gene (rs2235544) and DIO2 gene (rs12885300) have independent prognostic significance in glioblastoma patients. The C-allele of the DIO1 (rs2235544) is associated with greater T4 to T3 conversion.

Metabolomic profiling of blood plasma in patients with primary brain tumours: Basal plasma metabolites correlated with tumour grade and plasma biomarker analysis predicts feasibility of the successful statistical discrimination from healthy subjects - a preliminary study.

The brain tumours represent a complex tissue that has its own characteristic metabolic features and is interfaced with the whole organism. We investigated changes in basal blood plasma metabolites in the presence of primary brain tumour, their correlation with tumour grade, as well as the feasibility of statistical discrimination based on plasma metabolites. Together 60 plasma samples from patients with clinically defined glioblastoma, meningioma, oligodendrioglioma, astrocytoma, and non-specific glial tumour and plasma samples from 28 healthy volunteers without any cancer history were measured by NMR spectroscopy. In blood plasma of primary brain tumour patients, we found significantly increased levels of glycolytic metabolites glucose and pyruvate, and significantly decreased level of glutamine and also metabolites participating in tricarboxylic acid (TCA) cycle, citrate and succinate, when compared with controls. Further, plasma metabolites levels: tyrosine, phenylalanine, glucose, creatine and creatinine correlated significantly with tumour grade. In general, observed changes are parallel to the biochemistry expected for tumourous tissue and metabolic changes in plasma seem to follow the similar rules in all primary brain tumours, with very subtle variations among tumour types. Only two plasma metabolites tyrosine and phenylalanine were increased exclusively in blood plasma of patients with glioblastoma. Based on metabolite levels, an excellent discrimination between plasma from patient's tumours and controls was attainable. The metabolites creatine, pyruvate, glucose, formate, creatinine and citrate were of the highest discriminatory power.

Systemic management of malignant meningiomas: A comparative survival and molecular marker analysis between Octreotide in combination with Everolimus and Sunitinib.

PURPOSE: To compare the effectiveness of octreotide/everolimus vs. sunitinib for the systemic treatment of recurrent aggressive meningiomas. METHODS: 31 patients with recurrent or refractory WHO II or WHO III meningiomas were examined in two reference centers in Colombia. Patients who had systemic treatment (sunitinib, everolimus/octreotide) and a complete follow-up were included. Overall survival (OS), progression-free survival (PFS) and toxicities were evaluated. Additionally, tissue samples were examined for PDGFRß and VEGFR2, their expression was correlated with outcomes. RESULTS: Twenty-two patients (72%) were female with a median age of 55 years (SD±15.3). The most prevalent histology was anaplastic meningioma in 20 patients (65%) with 48% of patients suffering from three previous relapses before the start of systemic treatment. A total of 14 patients received combination therapy with octreotide/everolimus, 11 received sunitinib and the remaining 6 received other second-line agents. Median OS was 37.3 months (95%CI 28.5-42.1) and the PFS during the treatment with everolimus/octreotide (EO) and sunitinib (Su) was 12.1 months (95%CI 9.2-21.1) and 9.1 months (95%CI 6.8-16.8); p = 0.43), respectively. The OS of the group treated with the EO→Su→Bev sequence (1st/2nd/3rd line) was 6.5 months longer than the Su→EO→Bev sequence (36.0 vs. 29.5 months) (p = 0.0001). When analyzing molecular markers, the positive PDGFRß and negative VEGFR2 expression were associated with longer survival both in OS and PFS. CONCLUSION: Sunitinib and octreotide/everolimus have similar efficacy and safety in the systemic management of refractory meningioma. VEGFR2 and PDGFRß expression are associated with better outcomes.

Can Systemic Inflammatory Markers Be Used to Predict the Pathological Grade of Meningioma Before Surgery?

BACKGROUND: We sought to determine whether systemic inflammatory markers (SIMs) can be used to predict the pathological grade of meningioma before surgery. METHODS: Patients with histopathologically proven intracranial meningiomas who had undergone surgery from January 2014 to April 2018 were identified. The 14 most recent SIM levels measured before surgery were retrieved. The Mann-Whitney U test was used to determine the statistically significant differences between groups. Receiver operating characteristic curves were constructed, and the areas under the curve (AUC) were calculated to assess the diagnostic value of each biomarker. Predictive models built with biomarker pairs using logistic regression or support vector machine classifiers were used to assess their combined performance. RESULTS: A total of 672 patients with 575 and 97 low-grade and high-grade meningiomas, respectively, were investigated. Of the 14 SIMS, 7 differed significantly between the 2 meningioma groups. However, receiver operating characteristic analysis showed that none of these 7 SIMs alone could predict for the meningioma grade; the highest AUC was 0.61. Two biomarkers (erythrocyte and neutrophil/lymphocyte ratio) were incorporated into the logistic regression model; the corresponding AUC was 0.64. Moreover, 21 biomarker pairs were used to train the support vector machine classifiers; the AUCs of 6 pairs were >0.55; the maximum AUC was 0.60. CONCLUSIONS: SIMs obtained from routine preoperative laboratory testing had a limited ability to differentiate low- and high-grade meningioma in our cohort of 672 patients. Further prospective, multicenter studies with larger sample sizes are warranted to confirm this finding.

Serum Levels of APRIL Increase in Patients with Glioma, Meningioma and Schwannoma

Objective: Brain tumors are of high mortality and morbidity for which there is still no cure. The TNF family cytokine, A Proliferation Inducing Ligand (APRIL), is shown to help proliferation and development of tumor cells. We assessed serum levels of APRIL in patients with glioma, meningioma and schwannoma in comparison to healthy individuals. Methods: Peripheral blood samples of 68 patients with brain tumors, divided into three groups of gliomas (n=25), meningiomas (n=30) and schwannomas (n=13), as well as 45 healthy individuals were obtained. Serum samples were prepared and stored in -40°C until usage. Using a commercial ELISA method, APRIL concentration was measured in each serum sample. The obtained data were then analyzed using SPSS software. Results: APRIL serum levels were higher in all patients compared to the controls (P<0.001). Moreover, APRIL serum levels were higher in each of the tumor bearing groups (gliomas, meningiomas and schwannomas) in comparison to the controls (P<0.001, <0.001 and =0.001, respectively). Comparing APRIL between the patients groups showed no significant difference. Age and gender showed no significant correlation with serum APRIL levels, although the age of patients in glioma group was significantly lower than controls (P=0.017). The serum APRIL levels in gliomas with histological grade showed no difference, but in meningiomas, it was lower in tumors with higher grades (P= 0.011). Conclusion: Increased serum levels of APRIL in patients with meningioma and schwannoma as well as glioma may indicate a common role of this cytokine in brain tumors.

A comprehensive study of risk factors for post-operative pneumonia following resection of meningioma.

BACKGROUND: Post-operative pneumonia (Pop) following meningioma surgery is the dominant systemic complication which could cause serious threats to patients. It is unclear whether hematological biochemical markers are independently associated with the Pop. This study attempted to perform a more comprehensive study of taking both clinical factors and hematological biomarkers into account to promote the management of patients after meningioma surgery. METHODS: We collected clinical and hematological parameters of 1156 patients undergoing meningioma resection from January 2009 to January 2013. According to whether the symptoms of pneumonia had manifested,patients were divided into the Pop group and the Non-Pop group. We analyzed the distinctions of clinical factors between the two groups. We successively performed univariate and multivariate regression analysis to identify risk factors independently associated with the Pop. RESULTS: 4.4% patients infected with the Pop (51 of 1156). The median age at diagnosis of the Pop patients was significantly older than the Non-Pop group (p = 0.002). There were strike distinctions of post-operative hospital stays between two groups, with 21 days and 7 days each (p < 0.001). On multivariate analysis, tumor relapse (p < 0.001), skull base lesions (p = 0.001), intra-operative blood transfusion (p = 0.018) and cardiovascular diseases (p = 0.001) were linked with increased risk of the Pop following meningioma resection. For hematological biochemical markers, it was the factor of Red blood cell distribution width-standard deviation (RDW-SD) (OR 5.267, 95%CI 1.316, 21.078; p = 0.019) and Neutrophils lymphocytes ratio (NLR) (OR 2.081, 95%CI 1.063, 4.067; p = 0.033) that could appreciably predict the Pop. CONCLUSIONS: Apart from tumor recurrence, localizations, intra-operative blood transfusion and cardiovascular diseases are independent risk factors for the Pop. We initially found hematological RDW-SD and NLR are also important predictors.

Investigating the Levels of Soluble Extracellular Domain of HER2 Protein in the Sera of Meningioma Patients.

AIM: Bearing in mind the association of breast cancer and meningioma, the present study aimed to investigate the levels of the soluble extracellular domain of HER2 protein in meningioma cases and control group. Besides, in the present research, its associations with pathological features and prognostic indicators of meningioma were examined. MATERIAL AND METHODS: A total of 68 meningioma patients along with 20 healthy age-sex matched individuals, as controls, were selected. Levels of HER2 in the sera were measured by a quantitative enzyme-linked immunosorbent assay (ELISA). RESULTS: The observations showed that Serum HER2 levels in meningioma patients were significantly lower than normal controls. However, outlier quantities were mostly observed in the cases. Furthermore, in meningiomas with higher histological grade (grade II, III), statistically significant elevated serum levels of HER2 were observed compared to patients with low-grade meningiomas (grade I). CONCLUSION: Serum HER2 levels were a poor biomarker for determination of pathological and prognostic characteristics of meningiomas and coupling serum HER2 levels with immunohistochemistry examination of HER2 in meningioma tissue samples would be helpful in future studies.

Significance and Prognostic Value of The Coagulation Profile in Patients with Glioblastoma: Implications for Personalized Therapy.

BACKGROUND: Coagulation is an important aspect of the vascular microenvironment in which brain tumors evolve. Patients with tumor often show aberrant coagulation and fibrinolysis activation. In particular, glioblastoma (GBM), the most aggressive primary brain tumor, is associated with a state of hypercoagulability, and venous thromboembolism is a common complication of this cancer and its treatment. Our study aims to investigate the clinical and prognostic significance of routine laboratory tests to assess the coagulative state of patients with brain tumors, to identify potential new prognostic factors and targets for personalized therapy. METHODS: Blood samples were collected from patients with GBM (n = 58) and patients with meningioma (MNG, n = 22), before any treatment. The parameters analyzed were prothrombin time (PT), activated partial thromboplastin time (aPTT), D dimer (DD), fibrinogen, von Willebrand factor (VWF), leukocyte count, and hemoglobin levels. RESULTS: Plasma levels of PT and aPTT were significantly reduced in GBMs compared with MNGs (P < 0.05), whereas DD, VWF:Ag levels, and leukocyte count were significantly higher in GBMs than in MNGs (P < 0.01). Furthermore, we observed that patients with GBM with reduced PT and aPTT and high levels of DD and VWF, defined as hypercoagulable patients, showed reduced overall survival (P < 0.05) compared with nonhypercoagulable patients. CONCLUSIONS: Our data support the assumption that patients with GBM show a plasma hypercoagulable profile and that coagulation profile is related to adverse outcome in patients with GBM. If confirmed, hypercoagulability could play an important role as a prognostic factor of the disease and in the decision of an antithrombotic prophylaxis.

Serum TIMP1 and TIMP2 concentration in patients with different grades of meningioma.

OBJECTIVE: Meningiomas are common primary brain tumors that constitute about 13% of all intracranial tumors. Matrix metalloproteinase-9 (MMP-9) is able to degrade the extracellular matrix and basement membrane leading to cancer cell invasion and metastasis. MMPs are specifically inhibited by a family of small extracellular proteins known as the tissue inhibitors of metalloproteinases (TIMPs). The objective of this project was to evaluate serum concentration of TIMP-1 and TIMP-2 in patients with different grades of meningioma. PATIENTS AND METHODS: Ninety samples from different stages of patients with meningitis (42 cases of grade I, 28 grade II, 20 grade III) and 51 samples from normal healthy were included in this study. Total protein concentration (TPC) and the level TIMP-1 and TIMP-2 serum were determined by Bio-Rad protein assay based on the Bradford dye procedure and enzyme-linked immunosorbent assay (ELISA), respectively. RESULTS: No significant change in the TPC was seen in the serum of patients with meningioma when compared with normal controls. Results obtained demonstrated that all serum samples presented TIMP-1 and TIMP-2 expression, whereas, starting from grade I to III meningiomas, a significant decrease of TIMP-1 and TIMP-2 expression was observed as compared to controls. CONCLUSION: The results of this study show that a low expression of TIMP1 and TIMP2 is correlated with advanced stages of meningioma. It is also concluded that the detection of serum TIMP1 and TIMP2 may be useful in classifying different grades of meningioma.

An early investigative serum Raman spectroscopy study of meningioma.

Meningiomas represent one of the most frequently reported non-glial, primary brain and central nervous system (CNS) tumors. Meningiomas often display a spectrum of anomalous locations and morphological attributes, deterring their timely diagnosis. Majority of them are sporadic in nature and thus the present-day screening strategies, including radiological investigations, often result in misdiagnosis due to their aberrant and equivocal radiological facets. Therefore, it is pertinent to explore less invasive and patient-friendly biofluids such as serum for their screening and diagnostics. The utility of serum Raman spectroscopy in diagnosis and therapeutic monitoring of cancers has been reported in the literature. In the present study, for the first time, to the best of our knowledge, we have explored Raman spectroscopy to classify the sera of meningioma and control subjects. For this exploration, 35 samples each of meningioma and control subjects were accrued and the spectra revealed variance in the levels of DNA, proteins, lipids, amino acids and ß-carotene, i.e., a relatively higher protein, DNA and lipid content in meningioma. Subsequent Principal Component Analysis (PCA) and Principal Component-Linear Discriminant Analysis (PC-LDA) followed by Leave-One-Out Cross-Validation (LOOCV) and limited independent test data, in a patient-wise approach, yielded a classification efficiency of 92% and 80% for healthy and meningioma, respectively. Additionally, in the analogous analysis between healthy and different grades of meningioma, similar results were obtained. These results indicate the potential of Raman spectroscopy in differentiating meningioma. As present methods suffer from known limitations, with the prospective validation on a larger cohort, serum Raman spectroscopy could be an adjuvant/alternative approach in the clinical management of meningioma.

Prognostic role of high sensitivity C-reactive protein and interleukin-6 in glioma and meningioma patients.

High sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) can be important prognostic indicators of brain tumor patients. We investigated the association of circulating IL-6 and hsCRP concentrations with discharge outcomes and survival of glioma and meningioma patients. One-hundred and sixty-three (115 women; median age 57 years) patients admitted for meningioma (n = 94), high-grade glioma (n = 48) and low-grade glioma (n = 21) surgery were enrolled in this prospective cohort study. Serum samples were collected within 24 h of admission. Discharge outcome was evaluated using the Glasgow Outcome Scale (unfavorable outcome = score from 1 to 3). Follow-up continued until November, 2016. Elevated IL-6 (≥ 2 pg/ml) and hsCRP (≥ 1 mg/l) concentrations were present in 25 and 35% of brain tumor patients, respectively. Elevated IL-6 concentrations were associated with unfavorable outcome at hospital discharge, adjusting for brain tumor histological diagnosis, patient age and gender (OR 2.39, 95% CI 0.97-5.91, p = 0.05). Elevated hsCRP concentrations were not associated with discharge outcome (p = 0.13). In multivariate Cox regression analyses adjusted for patient age, gender, extent of tumor resection and adjuvant treatment, elevated IL-6 concentration was associated with greater mortality risk in high-grade glioma patients (OR 2.623; 95% CI 1.129-5.597; p = 0.01), while elevated hsCRP concentration was associated with greater mortality risk in meningioma patients (OR 3.650; 95% CI 1.038-12.831; p = 0.04). Elevated IL-6 concentration is associated with greater unfavorable outcome risk in brain tumor patients and with greater mortality in high-grade glioma patients, while elevated hsCRP concentration is associated with greater mortality in meningioma patients.