Astrocyte- and NMDA receptor-dependent slow inward currents differently contribute to synaptic plasticity in an age-dependent manner in mouse and human neocortex.

Slow inward currents (SICs) are known as excitatory events of neurons elicited by astrocytic glutamate via activation of extrasynaptic NMDA receptors. By using slice electrophysiology, we tried to provide evidence that SICs can elicit synaptic plasticity. Age dependence of SICs and their impact on synaptic plasticity was also investigated in both on murine and human cortical slices. It was found that SICs can induce a moderate synaptic plasticity, with features similar to spike timing-dependent plasticity. Overall SIC activity showed a clear decline with aging in humans and completely disappeared above a cutoff age. In conclusion, while SICs contribute to a form of astrocyte-dependent synaptic plasticity both in mice and humans, this plasticity is differentially affected by aging. Thus, SICs are likely to play an important role in age-dependent physiological and pathological alterations of synaptic plasticity.

[The effect of surgical psychoeducation on the outcome of spinal surgery]. / A mutéti felkészítés hatásának vizsgálata gerincmutétet követoen.

Background and purpose – Interdiscipli­ nary researches demonstrate that patients’ fears and anxieties about surgery play a key role in the success of postoperative recovery. Psychoeducation is a professional information transfer method that aims to increase patients’ knowledge about their dis­ ease, and how to cope with it, and to emo­ tionally process the problems associated with the disease. If patients feel competent in their own healing process after surgery, they will experience less pain and become self­sufficient sooner, thereby the number of nursing days spent in the clinic reduces.
Methods – In this study the effect of psycho-education before spinal surgery on the use of postoperative analgetics was investigated. Results – The drug consumption of the study group who had been previously administered patient education is significantly reduced in comparison the control group.
Conclusion – Cooperation of a psychologist in surgical therapy promotes early recovery of patients in physical and mental well­being and reduces the costs of rehabilitation as well.

MMP-9 as Prognostic Marker for Brain Tumours: A Comparative Study on Serum-Derived Small Extracellular Vesicles.

Matrix metalloproteinase-9 (MMP-9) degrades the extracellular matrix, contributes to tumour cell invasion and metastasis, and its elevated level in brain tumour tissues indicates poor prognosis. High-risk tissue biopsy can be replaced by liquid biopsy; however, the blood-brain barrier (BBB) prevents tumour-associated components from entering the peripheral blood, making the development of blood-based biomarkers challenging. Therefore, we examined the MMP-9 content of small extracellular vesicles (sEVs)-which can cross the BBB and are stable in body fluids-to characterise tumours with different invasion capacity. From four patient groups (glioblastoma multiforme, brain metastases of lung cancer, meningioma, and lumbar disc herniation as controls), 222 serum-derived sEV samples were evaluated. After isolating and characterising sEVs, their MMP-9 content was measured by ELISA and assessed statistically (correlation, paired t-test, Welch's test, ANOVA, ROC). We found that the MMP-9 content of sEVs is independent of gender and age, but is affected by surgical intervention, treatment, and recurrence. We found a relation between low MMP-9 level in sEVs (<28 ppm) and improved survival (8-month advantage) of glioblastoma patients, and MMP-9 levels showed a positive correlation with aggressiveness. These findings suggest that vesicular MMP-9 level might be a useful prognostic marker for brain tumours.

Mapping the functional expression of auxiliary subunits of KCa1.1 in glioblastoma.

Glioblastoma (GBM) is the most aggressive glial tumor, where ion channels, including KCa1.1, are candidates for new therapeutic options. Since the auxiliary subunits linked to KCa1.1 in GBM are largely unknown we used electrophysiology combined with pharmacology and gene silencing to address the functional expression of KCa1.1/ß subunits complexes in both primary tumor cells and in the glioblastoma cell line U-87 MG. The pattern of the sensitivity (activation/inhibition) of the whole-cell currents to paxilline, lithocholic acid, arachidonic acid, and iberiotoxin; the presence of inactivation of the whole-cell current along with the loss of the outward rectification upon exposure to the reducing agent DTT collectively argue that KCa1.1/ß3 complex is expressed in U-87 MG. Similar results were found using human primary glioblastoma cells isolated from patient samples. Silencing the ß3 subunit expression inhibited carbachol-induced Ca2+ transients in U-87 MG thereby indicating the role of the KCa1.1/ß3 in the Ca2+ signaling of glioblastoma cells. Functional expression of the KCa1.1/ß3 complex, on the other hand, lacks cell cycle dependence. We suggest that the KCa1.1/ß3 complex may have diagnostic and therapeutic potential in glioblastoma in the future.

Mitochondrial DNA copy number changes, heteroplasmy, and mutations in plasma-derived exosomes and brain tissue of glioblastoma patients.

Glioblastoma is the most common malignant tumor of the central nervous system (CNS) in adults. Glioblastoma cells show increased glucose consumption associated with poor prognosis. Since mitochondria play a crucial role in energy metabolism, mutations and copy number changes of mitochondrial DNA may serve as biomarkers. As the brain is difficult to access, analysis of mitochondria directly from the brain tissue represents a challenge. Exosome analysis is an alternative (still poorly explored) approach to investigate molecular changes in CNS tumors. We analyzed brain tissue DNA and plasma-derived exosomal DNA (exoDNA) of 44 glioblastoma patients and 40 control individuals. Quantitative real-time PCR was performed to determine mtDNA copy numbers and the Kruskal-Wallis and Mann-Whitney U test were used for statistical analysis of data. Subsequently, sequencing libraries were prepared and sequenced on the MiSeq platform to identify mtDNA point mutations. Tissue mtDNA copy number was different among controls and patients in multiple comparisons. A similar tendency was detected in exosomes. Based on NGS analysis, several mtDNA point mutations showed slightly different frequencies between cases and controls, but the clinical relevance of these observations is difficult to assess and likely less than that of overall mtDNA copy number changes. Allele frequencies of variants were used to determine the level of heteroplasmy (found to be higher in exo-mtDNA of control individuals). Despite the suggested potential, the use of such biomarkers for the screening and/or diagnosis of glioblastomas is still limited, thus further studies are needed.

Topographic mapping of the glioblastoma proteome reveals a triple-axis model of intra-tumoral heterogeneity.

Glioblastoma is an aggressive form of brain cancer with well-established patterns of intra-tumoral heterogeneity implicated in treatment resistance and progression. While regional and single cell transcriptomic variations of glioblastoma have been recently resolved, downstream phenotype-level proteomic programs have yet to be assigned across glioblastoma's hallmark histomorphologic niches. Here, we leverage mass spectrometry to spatially align abundance levels of 4,794 proteins to distinct histologic patterns across 20 patients and propose diverse molecular programs operational within these regional tumor compartments. Using machine learning, we overlay concordant transcriptional information, and define two distinct proteogenomic programs, MYC- and KRAS-axis hereon, that cooperate with hypoxia to produce a tri-dimensional model of intra-tumoral heterogeneity. Moreover, we highlight differential drug sensitivities and relative chemoresistance in glioblastoma cell lines with enhanced KRAS programs. Importantly, these pharmacological differences are less pronounced in transcriptional glioblastoma subgroups suggesting that this model may provide insights for targeting heterogeneity and overcoming therapy resistance.

Novel Concepts of Glioblastoma Therapy Concerning Its Heterogeneity.

Although treatment outcomes of glioblastoma, the most malignant central nervous system (CNS) tumor, has improved in the past decades, it is still incurable, and survival has only slightly improved. Advances in molecular biology and genetics have completely transformed our understanding of glioblastoma. Multiple classifications and different diagnostic methods were made according to novel molecular markers. Discovering tumor heterogeneity only partially explains the ineffectiveness of current anti-proliferative therapies. Dynamic heterogeneity secures resistance to combined oncotherapy. As tumor growth proceeds, new therapy-resistant sub clones emerge. Liquid biopsy is a new and promising diagnostic tool that can step up with the dynamic genetic change. Getting a 'real-time' picture of a specific tumor, anti-invasion and multi-target treatment can be designed. During invasion to the peri-tumoral brain tissue, glioma cells interact with the extracellular matrix components. The expressional levels of these matrix molecules give a characteristic pattern, the invasion spectrum, which possess vast diagnostical, predictive and prognostic information. It is a huge leap forward combating tumor heterogeneity and searching for novel therapies. Using the invasion spectrum of a tumor sample is a novel tool to distinguish between histological subtypes, specifying the tumor grades or different prognostic groups. Moreover, new therapeutic methods and their combinations are under trial. These are crucial steps towards personalized oncotherapy.

Analysis of Circulating miRNA Profile in Plasma Samples of Glioblastoma Patients.

(1) Background: Glioblastoma multiforme (GBM) is among the most aggressive cancers with a poor prognosis. Treatment options are limited, clinicians lack efficient prognostic and predictive markers. Circulating miRNAs-besides being important regulators of cancer development-may have potential as diagnostic biomarkers of GBM. (2) Methods: In this study, profiling of 798 human miRNAs was performed on blood plasma samples from 6 healthy individuals and 6 patients with GBM, using a NanoString nCounter Analysis System. To validate our results, five miRNAs (hsa-miR-433-3p, hsa-miR-362-3p, hsa-miR-195-5p, hsa-miR-133a-3p, and hsa-miR-29a-3p) were randomly chosen for RT-qPCR detection. (3) Results: In all, 53 miRNAs were significantly differentially expressed in plasma samples of GBM patients when data were filtered for FC 1 and FDR 0.1. Target genes of the top 39 differentially expressed miRNAs were identified, and we carried out functional annotation and pathway enrichment analysis of target genes via GO and KEGG-based tools. General and cortex-specific protein-protein interaction networks were constructed from the target genes of top miRNAs to assess their functional connections. (4) Conclusions: We demonstrated that plasma microRNA profiles are promising diagnostic and prognostic molecular biomarkers that may find an actual application in the clinical practice of GBM, although more studies are needed to validate our results.

Raman Spectral Signatures of Serum-Derived Extracellular Vesicle-Enriched Isolates May Support the Diagnosis of CNS Tumors.

Investigating the molecular composition of small extracellular vesicles (sEVs) for tumor diagnostic purposes is becoming increasingly popular, especially for diseases for which diagnosis is challenging, such as central nervous system (CNS) malignancies. Thorough examination of the molecular content of sEVs by Raman spectroscopy is a promising but hitherto barely explored approach for these tumor types. We attempt to reveal the potential role of serum-derived sEVs in diagnosing CNS tumors through Raman spectroscopic analyses using a relevant number of clinical samples. A total of 138 serum samples were obtained from four patient groups (glioblastoma multiforme, non-small-cell lung cancer brain metastasis, meningioma and lumbar disc herniation as control). After isolation, characterization and Raman spectroscopic assessment of sEVs, the Principal Component Analysis-Support Vector Machine (PCA-SVM) algorithm was performed on the Raman spectra for pairwise classifications. Classification accuracy (CA), sensitivity, specificity and the Area Under the Curve (AUC) value derived from Receiver Operating Characteristic (ROC) analyses were used to evaluate the performance of classification. The groups compared were distinguishable with 82.9-92.5% CA, 80-95% sensitivity and 80-90% specificity. AUC scores in the range of 0.82-0.9 suggest excellent and outstanding classification performance. Our results support that Raman spectroscopic analysis of sEV-enriched isolates from serum is a promising method that could be further developed in order to be applicable in the diagnosis of CNS tumors.

[The role of low grade glioma prognostic factors in therapeutic choices - summary of international literature and recommendations with conclusions]. / Az alacsony grádusú gliómák prognosztikai faktorainak szerepe a terápia megválasztásában ­ a nemzetközi irodalom és ajánlások összefoglalása konklúziókkal.

Our knowledge on low grade gliomas has grown extensively recently. Both molecular alterations and clinical trials unraveling their clinical significance are difficult to get familiar with. Thus, efforts made to reach any consensus are of upmost importance, so that multidisciplinary teams involved in patient management can make up-to-date, individually-tailored therapeutic plans. Our aims were to synthesize all the molecular and clinical investigations, recommendations and guidelines related to low grade gliomas in Hungarian language, and to define low and high risk prognostic groups with different therapeutic strategies. The roles of 21 molecular pathological markers and their significance levels in low grade gliomas are summarized in this paper. Data from relevant literature, as well as recommendations of neuro-oncological organizations were included. This summary could help to integrate diverse therapeutic plans of the past decades in low grade gliomas. Moreover, this paper may serve as a source for future revisions when updating low and high risk groups in low grade gliomas.

Histone H3.3G34-Mutant Interneuron Progenitors Co-opt PDGFRA for Gliomagenesis.

Histone H3.3 glycine 34 to arginine/valine (G34R/V) mutations drive deadly gliomas and show exquisite regional and temporal specificity, suggesting a developmental context permissive to their effects. Here we show that 50% of G34R/V tumors (n = 95) bear activating PDGFRA mutations that display strong selection pressure at recurrence. Although considered gliomas, G34R/V tumors actually arise in GSX2/DLX-expressing interneuron progenitors, where G34R/V mutations impair neuronal differentiation. The lineage of origin may facilitate PDGFRA co-option through a chromatin loop connecting PDGFRA to GSX2 regulatory elements, promoting PDGFRA overexpression and mutation. At the single-cell level, G34R/V tumors harbor dual neuronal/astroglial identity and lack oligodendroglial programs, actively repressed by GSX2/DLX-mediated cell fate specification. G34R/V may become dispensable for tumor maintenance, whereas mutant-PDGFRA is potently oncogenic. Collectively, our results open novel research avenues in deadly tumors. G34R/V gliomas are neuronal malignancies where interneuron progenitors are stalled in differentiation by G34R/V mutations and malignant gliogenesis is promoted by co-option of a potentially targetable pathway, PDGFRA signaling.

[Prognostic significance of invasion in glioblastoma]. / Az inváziós spektrum prognosztikai jelentôsége glioblastomában.

BACKGROUND AND PURPOSE: Glioblastoma is the most common malignant CNS tumor, its surgical removal is hindered by the tumors invasive nature, while current anti-tumor therapies show limited effectiveness - mean overall survival is 16-24 months. Some patients show minimal response towards standard oncotherapy, however there are no routinely available prognostic and predictive markers in clinical practice to identify the background of mentioned differences in prognosis. This research aims to identify the prognostic significance of invasion-related extracellular (ECM) components. METHODS: Patient groups with different prognoses were created (OS: group A <16 months, group B > 16 months), and internationally recognized prognostic markers (IDH1 mutation and MGMT promoter hyper-methylation) were tested in the flash-frozen tumor samples. Furthermore, the mRNA levels of 46 invasion-related ECM molecules were measured. RESULTS: Clinical data of the patients who have been operated on at the University of Debrecen Clinical Center Department of Neurosurgery and treated at the Department of Clinical Oncology showed no significant differences except for survival data (OS and PFS), and reoperation rate. All samples were IDH wild type. MGMT promoter hypermethylation rate showed significant differences (28.6% vs 68.8%). The expressional pattern of the invasion-related ECM molecules, i.e. the invasion spectrum also showed major differences, integrin ß2, cadherin-12, FLT4/VEGFR-3 and versican molecules having signficantly different mRNA levels. The accuracy of the inivasion spectrum was tested by statistical classifier, 83.3% of the samples was sorted correctly, PPV was 0.93. CONCLUSION: The difference found in the reoperation rate when comparing different prognostic groups aligns with literature data. MGMG promoter region methylation data in Hungarian samples has not been published yet, and further confirming current knowledge urges the implementation of MGMT promoter analysis in clinical practice. Studying the invasion spectrum provides extra information on tumors, as a prognostic marker it helps recognizing more aggressive tumors, and calls attention to the necessity of using anti-invasive agents in GBM therapies in the future.

Novel Molecular Markers in Glioblastoma-Benefits of Liquid Biopsy.

: Glioblastoma is a primary Central Nervous System (CNS) malignancy with poor survival. Treatment options are scarce and despite the extremely heterogeneous nature of the disease, clinicians lack prognostic and predictive markers to characterize patients with different outcomes. Certain immunohistochemistry, FISH, or PCR-based molecular markers, including isocitrate dehydrogenase1/2 (IDH1/2) mutations, epidermal growth factor receptor variant III (EGFRvIII) mutation, vascular endothelial growth factor overexpression (VEGF) overexpression, or (O6-Methylguanine-DNA methyltransferase promoter) MGMT promoter methylation status, are well-described; however, their clinical usefulness and accuracy is limited, and tumor tissue samples are always necessary. Liquid biopsy is a developing field of diagnostics and patient follow up in multiple types of cancer. Fragments of circulating nucleic acids are collected in various forms from different bodily fluids, including serum, urine, or cerebrospinal fluid in order to measure the quality and quantity of these markers. Multiple types of nucleic acids can be analyzed using liquid biopsy. Circulating cell-free DNA, mitochondrial DNA, or the more stable long and small non-coding RNAs, circular RNAs, or microRNAs can be identified and measured by novel PCR and next-generation sequencing-based methods. These markers can be used to detect the previously described alterations in a minimally invasive method. These markers can be used to differentiate patients with poor or better prognosis, or to identify patients who do not respond to therapy. Liquid biopsy can be used to detect recurrent disease, often earlier than using imaging modalities. Liquid biopsy is a rapidly developing field, and similarly to other types of cancer, measuring circulating tumor-derived nucleic acids from biological fluid samples could be the future of differential diagnostics, patient stratification, and follow up in the future in glioblastoma as well.

Small Extracellular Vesicles Isolated from Serum May Serve as Signal-Enhancers for the Monitoring of CNS Tumors.

Liquid biopsy-based methods to test biomarkers (e.g., serum proteins and extracellular vesicles) may help to monitor brain tumors. In this proteomics-based study, we aimed to identify a characteristic protein fingerprint associated with central nervous system (CNS) tumors. Overall, 96 human serum samples were obtained from four patient groups, namely glioblastoma multiforme (GBM), non-small-cell lung cancer brain metastasis (BM), meningioma (M) and lumbar disc hernia patients (CTRL). After the isolation and characterization of small extracellular vesicles (sEVs) by nanoparticle tracking analysis (NTA) and atomic force microscopy (AFM), liquid chromatography -mass spectrometry (LC-MS) was performed on two different sample types (whole serum and serum sEVs). Statistical analyses (ratio, Cohen's d, receiver operating characteristic; ROC) were carried out to compare patient groups. To recognize differences between the two sample types, pairwise comparisons (Welch's test) and ingenuity pathway analysis (IPA) were performed. According to our knowledge, this is the first study that compares the proteome of whole serum and serum-derived sEVs. From the 311 proteins identified, 10 whole serum proteins and 17 sEV proteins showed the highest intergroup differences. Sixty-five proteins were significantly enriched in sEV samples, while 129 proteins were significantly depleted compared to whole serum. Based on principal component analysis (PCA) analyses, sEVs are more suitable to discriminate between the patient groups. Our results support that sEVs have greater potential to monitor CNS tumors, than whole serum.

Prognosis and Treatment Outcomes of Patients Undergoing Resection of Brain Metastases from Breast Cancer.

BACKGROUND: Brain metastases from breast cancer have poor prognosis and are a challenge to treat. Multiple treatment options are available. Descriptive and prognostic data on breast cancer brain metastases is limited. PATIENTS AND METHODS: This study analyzed clinical data of patients who underwent surgical resection of one or more brain metastases. Histological and clinical characteristics, as well as treatment modalities, were analyzed. RESULTS: Initial tumor stage or grade was found not to correlate with the median time to developing brain metastases or survival. Human epidermal growth factor receptor 2 (HER2)-positive status was not associated with shorter median time to developing brain metastases. No correlation was found between the number of brain metastases and patient outcome. Results confirm the survival benefit of surgical resection with or without irradiation. CONCLUSION: Data showed that patients with HER2-positive and those with triple-negative breast cancer develop brain metastases at lower stages but not earlier after diagnosis, and survival is mostly dependent on treatment modality rather than histological subtype.

Recurrent noncoding U1 snRNA mutations drive cryptic splicing in SHH medulloblastoma.

In cancer, recurrent somatic single-nucleotide variants-which are rare in most paediatric cancers-are confined largely to protein-coding genes1-3. Here we report highly recurrent hotspot mutations (r.3A>G) of U1 spliceosomal small nuclear RNAs (snRNAs) in about 50% of Sonic hedgehog (SHH) medulloblastomas. These mutations were not present across other subgroups of medulloblastoma, and we identified these hotspot mutations in U1 snRNA in only <0.1% of 2,442 cancers, across 36 other tumour types. The mutations occur in 97% of adults (subtype SHHδ) and 25% of adolescents (subtype SHHα) with SHH medulloblastoma, but are largely absent from SHH medulloblastoma in infants. The U1 snRNA mutations occur in the 5' splice-site binding region, and snRNA-mutant tumours have significantly disrupted RNA splicing and an excess of 5' cryptic splicing events. Alternative splicing mediated by mutant U1 snRNA inactivates tumour-suppressor genes (PTCH1) and activates oncogenes (GLI2 and CCND2), and represents a target for therapy. These U1 snRNA mutations provide an example of highly recurrent and tissue-specific mutations of a non-protein-coding gene in cancer.

Influence of Oncotherapy and Clinical Parameters on Survival of Glioblastoma Patients: A Single Center Experience.

BACKGROUND: Routine administration of temozolomide (TMZ) in the treatment protocol of glioblastoma in the last few years resulted in improving survival parameters of these patients but efficacy of supplementary bevacizumab (BVC) monotherapy has not been evidently proven. In this study, the effectiveness of different postoperative therapy for glioblastoma patients treated in our institute was evaluated. In addition, the prognostic value of clinical parameters on survival was also analyzed. METHODS: Accordance of clinical parameters (age, gender, tumor localization, size, side, Karnofsky performance score, and extension of tumor removal), postoperative treatment (radiotherapy [RT], RT + TMZ, RT + TMZ + BVC), and survival data were tested by 104 patients operated on glioblastoma in the Department of Neurosurgery, University of Debrecen between 2002 and 2012. RESULTS: Concurrent chemo-RT resulted in significant longer overall survival (OS) than RT alone (PRTvs.RT + TMZ = 0.0219) and BVC treatment after progression during TMZ also elongated survival significantly (PRT vs. RT + TMZ + BVC < 0.0001; PRT + TMZvs.RT + TMZ + BVC = 0.0022), respectively. Clinical parameters showed no significant influence on OS in comparison with different methods of postoperative oncotherapy. CONCLUSIONS: Both TMZ and BVC had a beneficial effect on glioblastoma patients' survival, but tested clinical parameters showed no evident accordance with final outcome. Although neurosurgery has an indispensable role in resecting space occupying tumors and providing good postoperative performance score patients for oncotherapy, the survival of glioblastoma patients depends rather on radio- and chemo-sensitivity than tested clinical parameters.

Significance of liquid biopsy in glioblastoma - A review.

Glioblastoma (GBM) is the most common and most aggressive primary malignant brain tumor with a 16-24 -months overall survival time (OS). Effective management is hindered by intratumoral heterogeneity, a characteristic trait of GBM which results in subpopulations of cells with altered therapeutic responsiveness, different invasiveness and growth potential. Correct initial molecular profiling of the tumor, as well as following its molecular biological changes are further impeded by the intracranial location of the tumors, hence the risks of surgical interventions. Radiological examination, the sole non-invasive method of obtaining information about the tumors, also has limitations. This review article aims to summarize the currently available information about the promising applicability of liquid biopsy, extracellular vesicles (EVs), and circulating cell-free nucleic acids (cf-NAs) in GBM patients. Liquid biopsy is a quick and inexpensive way of obtaining exceptionally relevant information about tumors, and can be performed multiple times during the clinical course of the disease. Furthermore, integrating analyses of EVs and related cf-NAs in clinical practice might also help to establish diagnosis in a non-invasive manner, and complex oncotherapy could be indicated in the future without high-risk neurosurgical interventions.

Extracellular matrix differences in glioblastoma patients with different prognoses.

Glioblastoma is the most common malignant central nervous system tumor. Patient outcome remains poor despite the development of therapy and increased understanding of the disease in the past decades. Glioma cells invade the peritumoral brain, which results in inevitable tumor recurrence. Previous studies have demonstrated that the extracellular matrix (ECM) is altered in gliomas and serves a major role in glioma invasion. The present study focuses on differences in the ECM composition of tumors in patients with poor and improved prognosis. The mRNA and protein expression of 16 invasion-associated ECM molecules was determined using reverse trascription-quantitiative polymerase chain reaction and immunohistochemistry, respectively. Clinical factors of patients with different prognoses was also analyzed. It was determined that age and postoperative Karnofsky performance score were associated with patient survival. Furthermore, Fms-related tyrosine kinase 4/vascular endothelial growth factor receptor 3 (FLT4/VEGFR3), murine double minute 2 (MDM2) and matrix metallopeptidase 2 (MMP2) mRNA levels were significantly different between the two prognostic groups. Additionally, brevican, cluster of differentiation 44, hyaluronan mediated motility receptor, integrin-αV and -ß1, and MDM2 protein expression were indicated to be significantly different in immunohistochemistry slides. Using the expression profile, including the invasion spectrum of the samples, it was possible to identify the prognostic group of the sample with high efficacy, particularly in cases with poor prognosis. In conclusion, it was determined that ECM components exhibit different expression levels in tumors with different prognoses and thus the invasion spectrum can be used as a prognostic factor in glioblastoma.

The Expressional Pattern of Invasion-Related Extracellular Matrix Molecules in CNS Tumors.

Aim of the study: Astrocytomas are primary CNS malignancies which infiltrate the peritumoral tissue, even when they are low-grade. Schwannomas are also primary CNS tumors, however, they do not show peritumoral infiltration similarly to brain metastases which almost never invade the neighboring parts of brain. Extracellular matrix is altered in composition in various cancer types and is proposed to play an important role in the development of invasiveness of astrocytic tumors. This study aims to identify differences in the ECM composition of CNS tumors with different invasiveness.Materials and methods: The mRNA and protein levels of ECM components were measured by QRT-PCR and mass-spectrometry, respectively, in grade II astrocytoma, NSCLC brain metastasis, schwannomas, and non-tumor brain control samples. Expressional data was analyzed statistically with ANOVA and nearest neighbor search.Results: There is a significant difference in the expressional pattern of invasion-related ECM components among various CNS tumors, especially among those of different embryonic origin. Non-invasive tumors show only slight differences in the expressional pattern of ECM molecules. Tumor samples can be separated based on their expressional pattern using statistical classifiers, therefore the ECM composition seems to be typical of various cancer types.Conclusions: Differences in the expressional pattern of the ECM could be responsible for the different invasiveness of various CNS tumors.