Migration of atrial catheter of ventriculo-cysto-atrial shunt into heart and pulmonary artery - case report and literature review.

Ventriculoatrial shunts are the alternative treatments when it is impossible to use ventriculoperitoneal shunts. Limited indication for ventriculoatrial shunt is due to the possibility of very serious complications inherent with this procedure. We present a case report of a young patient who suffered from disconnection of an atrial catheter from the valve after an accidental blow to his neck. The atrial catheter was dislocated to the heart and pulmonary artery and it was extracted through the femoral vein in the groin area using an endovascular technique. The procedure went without complications. A new atrial catheter was introduced under ultrasonic guidance during surgical revision.

11C-methionine in the diagnostics and management of glioblastoma patients with rapid early progression: nonrandomized, open label, prospective clinical trial (GlioMET).

BACKGROUND: Glioblastoma (GBM) is the most common and aggressive primary brain cancer. The treatment of GBM consists of a combination of surgery and subsequent oncological therapy, i.e., radiotherapy, chemotherapy, or their combination. If postoperative oncological therapy involves irradiation, magnetic resonance imaging (MRI) is used for radiotherapy treatment planning. Unfortunately, in some cases, a very early worsening (progression) or return (recurrence) of the disease is observed several weeks after the surgery and is called rapid early progression (REP). Radiotherapy planning is currently based on MRI for target volumes definitions in many radiotherapy facilities. However, patients with REP may benefit from targeting radiotherapy with other imaging modalities. The purpose of the presented clinical trial is to evaluate the utility of 11C-methionine in optimizing radiotherapy for glioblastoma patients with REP. METHODS: This study is a nonrandomized, open-label, parallel-setting, prospective, monocentric clinical trial. The main aim of this study was to refine the diagnosis in patients with GBM with REP and to optimize subsequent radiotherapy planning. Glioblastoma patients who develop REP within approximately 6 weeks after surgery will undergo 11C-methionine positron emission tomography (PET/CT) examinations. Target volumes for radiotherapy are defined using both standard planning T1-weighted contrast-enhanced MRI and PET/CT. The primary outcome is progression-free survival defined using RANO criteria and compared to a historical cohort with REP treated without PET/CT optimization of radiotherapy. DISCUSSION: PET is one of the most modern methods of molecular imaging. 11C-Methionine is an example of a radiolabelled (carbon 11) amino acid commonly used in the diagnosis of brain tumors and in the evaluation of response to treatment. Optimized radiotherapy may also have the potential to cover those regions with a high risk of subsequent progression, which would not be identified using standard-of-care MRI for radiotherapy planning. This is one of the first study focused on radiotherapy optimization for subgroup of patinets with REP. TRIAL REGISTRATION: NCT05608395, registered on 8.11.2022 in clinicaltrials.gov; EudraCT Number: 2020-000640-64, registered on 26.5.2020 in clinicaltrialsregister.eu. Protocol ID: MOU-2020-01, version 3.2, date 18.09.2020.

Neurosurgical treatment and outcome patterns in patients with meningioma in South Moravian region-a population-based study.

INTRODUCTION: Meningiomas are usually slow-growing tumours, constituting about one third of all primary intracranial tumours. They occur more frequently in women. Clinical manifestation of meningiomas depends on their location, tumour size and growth rate. In most cases, surgical treatment is the procedure of choice. The success of this treatment is, however, associated with the radicality of the resection. Radiotherapy represents an additional or alternative treatment modality. Gamma knife surgery is another notable treatment method, especially in small and/or slow-growing tumours in eloquent areas or in elderly patients. MATERIAL AND METHODS: Authors describe their experience with the diagnosis, treatment and outcome of the patients with meningioma (n = 857). Furthermore, they also assess the postoperative morbidity/mortality and recurrence rate. RESULTS AND CONCLUSIONS: In view of the benign histology of meningiomas, the success of the treatment largely depends (besides the tumour grading) on the radicality of the resection. The emphasis is also put on appropriate follow-up of the patients. In certain patients, the watch and wait strategy should be also considered as a suitable treatment method.

Effects of Reoperation Timing on Survival among Recurrent Glioblastoma Patients: A Retrospective Multicentric Descriptive Study.

Glioblastoma inevitably recurs, but no standard regimen has been established for treating this recurrent disease. Several reports claim that reoperative surgery can improve survival, but the effects of reoperation timing on survival have rarely been investigated. We, therefore, evaluated the relationship between reoperation timing and survival in recurrent GBM. A consecutive cohort of unselected patients (real-world data) from three neuro-oncology cancer centers was analyzed (a total of 109 patients). All patients underwent initial maximal safe resection followed by treatment according to the Stupp protocol. Those meeting the following criteria during progression were indicated for reoperation and were further analyzed in this study: (1) The tumor volume increased by >20-30% or a tumor was rediscovered after radiological disappearance; (2) The patient's clinical status was satisfactory (KS ≥ 70% and PS WHO ≤ gr. 2); (3) The tumor was localized without multifocality; (4) The minimum expected tumor volume reduction was above 80%. A univariate Cox regression analysis of postsurgical survival (PSS) revealed a statistically significant effect of reoperation on PSS from a threshold of 16 months after the first surgery. Cox regression models that stratified the Karnofsky score with age adjustment confirmed a statistically significant improvement in PSS for time-to-progression (TTP) thresholds of 22 and 24 months. The patient groups exhibiting the first recurrence at 22 and 24 months had better survival rates than those exhibiting earlier recurrences. For the 22-month group, the HR was 0.5 with a 95% CI of (0.27, 0.96) and a p-value of 0.036. For the 24-month group, the HR was 0.5 with a 95% CI of (0.25, 0.96) and a p-value of 0.039. Patients with the longest survival were also the best candidates for repeated surgery. Later recurrence of glioblastoma was associated with higher survival rates after reoperation.

Epidural Hematoma, a Rare Complication After the Use of Mayfield Clamp: A Case Report and Review of the Literature.

Herein, we describe a case of epidural hematoma associated with the use of a Mayfield head clamp. An 18-year old patient with an upper brainstem tumour causing obstructive hydrocephalus underwent a routine third ventriculostomy, which unexpectedly revealed an intracranial hemorrhage. We outline potential risk factors, propose an algorithm for preventing complications associated with the use of pin-type fixation, and conducted a structured review of the literature to identify similar clinical scenarios.

HLA-E and HLA-F Are Overexpressed in Glioblastoma and HLA-E Increased After Exposure to Ionizing Radiation.

BACKGROUND/AIM: Glioblastoma (GBM) is one of the deadliest human cancers responding very poorly to therapy. Although the central nervous system has been traditionally considered an immunologically privileged site with an enhanced immune response, GBM appears to benefit from this immunosuppressive milieu. Immunomodulatory molecules play an important role in immune tumor-host interactions. Non-classical human leukocyte antigens (HLA) class Ib molecules HLA-E, HLA-F, and HLA-G have been previously described to be involved in protecting semi-allogeneic fetal allografts from the maternal immune response and in transplant tolerance as well as tumoral immune escape. Unfortunately, their role in GBM remains poorly understood. Our study, therefore, aimed to characterize the relationship between the expression of these molecules in GBM on the transcriptional level and clinicopathological and molecular features of GBM as well as the effect of ionizing radiation. MATERIALS AND METHODS: We performed the analysis of HLA-E, HLA-F, and HLA-G mRNA expression in 69 GBM tissue samples and 21 non-tumor brain tissue samples (controls) by reverse transcription polymerase chain reaction. Furthermore, two primary GBM cell cultures had been irradiated to identify the effect of ionizing radiation on the expression of non-classical HLA molecules. RESULTS: Analyses revealed that both HLA-E and HLA-F are significantly up-regulated in GBM samples. Subsequent survival analysis showed a significant association between low expression of HLA-E and shorter survival of GBM patients. The dysregulated expression of both molecules was also observed between patients with methylated and unmethylated O-6-methylguanine-DNA methyltransferase (MGMT) promoter. Finally, we showed that ionizing radiation increased HLA-E expression level in GBM cells in vitro. CONCLUSION: HLA-E and HLA-F play an important role in GBM biology and could be used as diagnostic biomarkers, and in the case of HLA-E also as a prognostic biomarker.

Small RNA Sequencing Identifies PIWI-Interacting RNAs Deregulated in Glioblastoma-piR-9491 and piR-12488 Reduce Tumor Cell Colonies In Vitro.

Glioblastoma (GBM) is the most frequently occurring primary malignant brain tumor of astrocytic origin. To change poor prognosis, it is necessary to deeply understand the molecular mechanisms of gliomagenesis and identify new potential biomarkers and therapeutic targets. PIWI-interacting RNAs (piRNAs) help in maintaining genome stability, and their deregulation has already been observed in many tumors. Recent studies suggest that these molecules could also play an important role in the glioma biology. To determine GBM-associated piRNAs, we performed small RNA sequencing analysis in the discovery set of 19 GBM and 11 non-tumor brain samples followed by TaqMan qRT-PCR analyses in the independent set of 77 GBM and 23 non-tumor patients. Obtained data were subsequently bioinformatically analyzed. Small RNA sequencing revealed 58 significantly deregulated piRNA molecules in GBM samples in comparison with non-tumor brain tissues. Deregulation of piR-1849, piR-9491, piR-12487, and piR-12488 was successfully confirmed in the independent groups of patients and controls (all p < 0.0001), and piR-9491 and piR-12488 reduced GBM cells' ability to form colonies in vitro. In addition, piR-23231 was significantly associated with the overall survival of the GBM patients treated with Stupp regimen (p = 0.007). Our results suggest that piRNAs could be a novel promising diagnostic and prognostic biomarker in GBM potentially playing important roles in gliomagenesis.

Pre-Radiotherapy Progression after Surgery of Newly Diagnosed Glioblastoma: Corroboration of New Prognostic Variable.

BACKGROUND: The aim of this retrospective study is to assess the incidence, localization, and potential predictors of rapid early progression (REP) prior to initiation of radiotherapy in newly diagnosed glioblastoma patients and to compare survival outcomes in cohorts with or without REP in relation to the treatment. METHODS: We assessed a consecutive cohort of 155 patients with histologically confirmed irradiated glioblastoma from 1/2014 to 12/2017. A total of 90 patients with preoperative, postoperative, and planning MRI were analyzed. RESULTS: Median age 59 years, 59% men, and 39 patients (43%) underwent gross total tumor resection. The Stupp regimen was indicated to 64 patients (71%); 26 patients (29%) underwent radiotherapy alone. REP on planning MRI performed shortly prior to radiotherapy was found in 46 (51%) patients, most often within the surgical cavity wall, and the main predictor for REP was non-radical surgery (p < 0.001). The presence of REP was confirmed as a strong negative prognostic factor; median overall survival (OS) in patients with REP was 10.7 vs. 18.7 months and 2-year survival was 15.6% vs. 37.7% (hazard ratio HR 0.53 for those without REP; p = 0.007). Interestingly, the REP occurrence effect on survival outcome was significantly different in younger patients (≤ 50 years) and older patients (> 50 years) for OS (p = 0.047) and non-significantly for PFS (p = 0.341). In younger patients, REP was a stronger negative prognostic factor, probably due to more aggressive behavior. Patients with REP who were indicated for the Stupp regimen had longer OS compared to radiotherapy alone (median OS 16.0 vs 7.5; HR = 0.5, p = 0.022; 2-year survival 22.3% vs. 5.6%). The interval between surgery and the initiation of radiotherapy were not prognostic in either the entire cohort or in patients with REP. CONCLUSION: Especially in the subgroup of patients without radical resection, one may recommend as early initiation of radiotherapy as possible. The phenomenon of REP should be recognized as an integral part of stratification factors in future prospective clinical trials enrolling patients before initiation of radiotherapy.

Real-World Evidence in Glioblastoma: Stupp's Regimen After a Decade.

The aim of this retrospective study is to provide real-world evidence in glioblastoma treatment and to compare overall survival after Stupp's regimen treatment today and a decade ago. A current consecutive cohort of histologically confirmed glioblastoma irradiated from 1/2014 to 12/2017 in our cancer center was compared with an already published historical control of patients treated in 1/2003-12/2009. A total of new 155 patients was analyzed, median age 60.9 years, 61% men, 58 patients (37%) underwent gross total tumor resection. Stupp's regimen was indicated in 90 patients (58%), 65 patients (42%) underwent radiotherapy alone. Median progression-free survival in Stupp's regimen cohort was 6.7 months, median OS 16.0 months, and 2-year OS 30.7%. OS was longer if patients were able to finish at least three cycles of adjuvant chemotherapy (median 23.3 months and 43.9% of patients lived at 2 years after surgery). Rapid early progression prior to radiotherapy was a negative prognostic factor with HR 1.87 (p = 0.007). The interval between surgery and the start of radiotherapy (median 6.7 weeks) was not prognostically significant (p = 0.825). The median OS in the current cohort was about 2 months longer than in the historical control group treated 10 years ago (16 vs. 13.8 months) using the same Stupp's regimen. Taking into account differences in patient's characteristics between current and historical cohorts, age, extent of resection, and ECOG patient performance status adjusted HR (Stupp's regimen vs. RT alone) for OS was determined as 0.45 (p = 0.002).

Targeted Radiotherapy of the Tumor Cavity after Surgical Resection of Aggressive Recurrent Brain Metastasis: A Case Report.

Postoperative management of patients with brain metastases is controversial. Besides local control, cognitive function and quality of life are the most important outcomes of postoperative radiotherapy. In this case report, we introduce a patient with aggressive recurred solid metastasis treated with repeated surgery and an individual radiotherapy approach in order to highlight that close mutual collaboration leads to a clear benefit for our patients. The local targeted radiotherapy with 35 Gy in 10 fractions was performed with the volumetric modulated arc technique, leading to more than 2.5 years of local control and survival without any of the side effects usually attributed to whole brain radiotherapy.

Cerebrospinal Fluid MicroRNA Signatures as Diagnostic Biomarkers in Brain Tumors.

Central nervous system (CNS) malignancies include primary tumors that originate within the CNS as well as secondary tumors that develop as a result of metastatic spread. Circulating microRNAs (miRNAs) were found in almost all human body fluids including cerebrospinal fluid (CSF), and they seem to be highly stable and resistant to even extreme conditions. The overall aim of our study was to identify specific CSF miRNA patterns that could differentiate among brain tumors. These new biomarkers could potentially aid borderline or uncertain imaging results onto diagnosis of CNS malignancies, avoiding most invasive procedures such as stereotactic biopsy or biopsy. In total, 175 brain tumor patients (glioblastomas, low-grade gliomas, meningiomas and brain metastases), and 40 non-tumor patients with hydrocephalus as controls were included in this prospective monocentric study. Firstly, we performed high-throughput miRNA profiling (Illumina small RNA sequencing) on a discovery cohort of 70 patients and 19 controls and identified specific miRNA signatures of all brain tumor types tested. Secondly, validation of 9 candidate miRNAs was carried out on an independent cohort of 105 brain tumor patients and 21 controls using qRT-PCR. Based on the successful results of validation and various combination patterns of only 5 miRNA levels (miR-30e, miR-140, let-7b, mR-10a and miR-21-3p) we proposed CSF-diagnostic scores for each tumor type which enabled to distinguish them from healthy donors and other tumor types tested. In addition to this primary diagnostic tool, we described the prognostic potential of the combination of miR-10b and miR-196b levels in CSF of glioblastoma patients. In conclusion, we performed the largest study so far focused on CSF miRNA profiling in patients with brain tumors, and we believe that this new class of biomarkers have a strong potential as a diagnostic and prognostic tool in these patients.

MicroRNAs in Cerebrospinal Fluid as Biomarkers in Brain Tumor Patients.

Backround: Although central nervous system (CNS) tumors are not the most common cancers, their incidence rate is constantly growing. Unfortunately, this group of cancers is characterized by a very poor prognosis with a very short average patient survival. Appropriate therapy depends on early and accurate diagnosis. However, this is often limited by brain tumor localization and heterogeneity. Therefore, new diagnostic approaches and biomarkers that are robust, sensitive, specific, and also without need of invasive biopsy, are still being sought. Cerebrospinal fluid (CSF) comes into direct contact with the CNS and becomes a suitable source of biological material that could reflect actual state of CNS. Suitable molecules in this regard appear to be microRNAs (miRNAs), short non-coding RNAs, that have been already detected in CSF and whose dysregulated levels are associated with various types of brain tumors. Purpose: Unfortunately, the methodical approaches used for CSF miRNA analysis have not been sufficiently standardized yet. For this reason, we summarize and evaluate methodical approaches which were previously used for miRNA analysis from CSF in order to find the most appropriate ones. Subsequently, we review studies focused on miRNA with potential to become biomarkers of CNS tumors in the future. Supported by Ministry of Health of the Czech Republic, grants No. 15-34553A and 15-33158A. All rights reserved. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 3. 1. 2019 Accepted: 3. 1. 2019.

MicroRNA isolation and quantification in cerebrospinal fluid: A comparative methodical study.

Associated with the pathogenesis of many cancers, including brain tumors, microRNAs (miRNAs) present promising diagnostic biomarkers. These molecules have been also studied in cerebrospinal fluid (CSF), showing great potential as a diagnostic tool in patients with brain tumors. Even though there are some biological and technological factors that could affect the results and their biological and clinical interpretation, miRNA analysis in CSF is not fully standardized. This study aims to compare several RNA extraction and miRNA quantification approaches, including high-throughput technologies and individual miRNA detection methods, thereby contributing to the optimization and standardization of quantification of extracellular miRNAs in CSF. Such knowledge is essential for the potential use of miRNAs as diagnostic biomarkers in brain tumors.

Identification of microRNAs differentially expressed in glioblastoma stem-like cells and their association with patient survival.

Glioblastoma stem-like cells (GSCs) are critical for the aggressiveness and progression of glioblastoma (GBM) and contribute to its resistance to adjuvant treatment. MicroRNAs (miRNAs) are small, non-coding RNAs controlling gene expression at the post-transcriptional level, which are known to be important regulators of the stem-like features. Moreover, miRNAs have been previously proved to be promising diagnostic biomarkers in several cancers including GBM. Using global expression analysis of miRNAs in 10 paired in-vitro as well as in-vivo characterized primary GSC and non-stem glioblastoma cultures, we identified a miRNA signature associated with the stem-like phenotype in GBM. 51 most deregulated miRNAs classified the cell cultures into GSC and non-stem cell clusters and identified a subgroup of GSC cultures with more pronounced stem-cell characteristics. The importance of the identified miRNA signature was further supported by demonstrating that a Risk Score based on the expression of seven miRNAs overexpressed in GSC predicted overall survival in GBM patients in the TCGA dataset independently of the IDH1 status. In summary, we identified miRNAs differentially expressed in GSCs and described their association with GBM patient survival. We propose that these miRNAs participate on GSC features and could represent helpful prognostic markers and potential therapeutic targets in GBM.

Cerebrospinal fluid microRNAs as diagnostic biomarkers in brain tumors.

Cerebrospinal fluid (CSF) is a body fluid that has many important functions and is in direct contact with the extracellular environment of the central nervous system (CNS). CSF serves as both the communication channel allowing the distribution of various substances among the CNS cells and the storage facility for the waste products these cells release. For these reasons, CSF is a potential source of diagnostic biomarkers of many CNS diseases, including brain tumors. Recent studies have revealed that CSF also contains circulating microRNAs (miRNAs), short non-coding RNAs that have been described as biomarkers in many cancers. However, CSF miRNAs are difficult to detect, which is why researchers face major challenges, including technological difficulties in its detection and its lack of standardization. Therefore, this review aims (i) to highlight the potential of CSF miRNAs as diagnostic, prognostic and predictive biomarkers in brain tumors, and (ii) to summarize technological approaches for detection of CSF miRNAs.

Global MicroRNA Expression Profiling Identifies Unique MicroRNA Pattern of Radioresistant Glioblastoma Cells.

Glioblastoma multiforme (GBM) is the most aggressive intracranial tumor characterized with infaust prognosis. Despite advances in neurosurgical and radiotherapeutic techniques and chemotherapy, the median overall survival ranges between 12-15 months from diagnosis. The main cause of treatment failure is considered the presence of tumor cells resistant to conventional therapy, mainly radiotherapy. MicroRNAs (miRNAs) are small, non-coding RNAs that function as post-transcriptional regulators of gene expression and have been repeatedly proven to play important roles in pathogenesis and biological features of many cancers, including GBM and its radioresistant phenotype. In our study, we established radioresistant cells from the commonly used human GBM cell lines T98G, U87MG and U251. Consequently, we performed global miRNA expression profiling in both radioresistant and parental cell lines and identified 113 miRNAs with significantly different expression (p<0.05) between these two groups (73 miRNAs were up-regulated, 40 miRNAs were down-regulated). Some of these miRNAs have been previously described in relation to ionizing radiation, and others were herein identified for the first time. We believe that after deeper functional investigation of identified miRNAs in relation to radioresistance, these miRNAs present potential predictive biomarkers or therapeutic targets in GBM.

MiR-338-5p sensitizes glioblastoma cells to radiation through regulation of genes involved in DNA damage response.

Glioblastoma multiforme (GBM) is the most aggressive form of brain tumor. Despite radical surgery and radiotherapy supported by chemotherapy, the disease still remains incurable with an extremely low median survival rate of 12-15 months from the time of initial diagnosis. The main cause of treatment failure is considered to be the presence of cells that are resistant to the treatment. MicroRNAs (miRNAs) as regulators of gene expression are involved in the tumor pathogenesis, including GBM. MiR-338 is a brain-specific miRNA which has been described to target pathways involved in proliferation and differentiation. In our study, miR-338-3p and miR-338-5p were differentially expressed in GBM tissue in comparison to non-tumor brain tissue. Overexpression of miR-338-3p with miRNA mimic did not show any changes in proliferation rates in GBM cell lines (A172, T98G, U87MG). On the other hand, pre-miR-338-5p notably decreased proliferation and caused cell cycle arrest. Since radiation is currently the main treatment modality in GBM, we combined overexpression of pre-miR-338-5p with radiation, which led to significantly decreased cell proliferation, increased cell cycle arrest, and apoptosis in comparison to irradiation-only cells. To better elucidate the mechanism of action, we performed gene expression profiling analysis that revealed targets of miR-338-5p being Ndfip1, Rheb, and ppp2R5a. These genes have been described to be involved in DNA damage response, proliferation, and cell cycle regulation. To our knowledge, this is the first study to describe the role of miR-338-5p in GBM and its potential to improve the sensitivity of GBM to radiation.

Risk Score based on microRNA expression signature is independent prognostic classifier of glioblastoma patients.

Glioblastoma multiforme (GBM) is the most malignant primary brain tumor. The prognosis of GBM patients varies considerably and the histopathological examination is not sufficient for individual risk estimation. MicroRNAs (miRNAs) are small, non-coding RNAs that function as post-transcriptional regulators of gene expression and were repeatedly proved to play important roles in pathogenesis of GBM. In our study, we performed global miRNA expression profiling of 58 glioblastoma tissue samples obtained during surgical resections and 10 non-tumor brain tissues. The subsequent analysis revealed 28 significantly deregulated miRNAs in GBM tissue, which were able to precisely classify all examined samples. Correlation with clinical data led to identification of six-miRNA signature significantly associated with progression free survival [hazard ratio (HR) 1.98, 95% confidence interval (CI) 1.33-2.94, P < 0.001] and overa+ll survival (HR 2.86, 95% CI 1.91-4.29, P < 0.001). O(6)-methylguanine-DNA methyltransferase methylation status was evaluated as reference method and Risk Score based on six-miRNA signature indicated significant superiority in prediction of clinical outcome in GBM patients. Multivariate Cox analysis indicated that the Risk Score based on six-miRNA signature is an independent prognostic classifier of GBM patients. We suggest that the Risk Score presents promising prognostic algorithm with potential for individualized treatment decisions in clinical management of GBM patients.

MicroRNAs involved in chemo- and radioresistance of high-grade gliomas.

High-grade gliomas (HGGs) are malignant primary brain tumors of glial cell origin. Despite optimal course of treatment, including maximal surgical resection followed by adjuvant chemo- and/or radiotherapy, the prognosis still remains poor. The main reason is the commonly occurring chemo- and radioresistance of these tumors. In recent years, several signaling pathways, especially PI3K/AKT and ATM/CHK2/p53, have been linked to the resistance of gliomas. Moreover, additional studies have shown that these pathways are significantly regulated by microRNAs (miRNAs), short endogenous RNA molecules that modulate gene expression and control many biological processes including apoptosis, proliferation, cell cycle, invasivity, and angiogenesis. MiRNAs are not only highly deregulated in gliomas, their expression signatures have also been shown to predict prognosis and therapy response. Therefore, they present promising biomarkers and therapeutic targets that might overcome the resistance to treatment and improve prognosis of glioma patients. In this review, we summarize the current knowledge of the functional role of miRNAs in gliomas resistance to chemo- and radiotherapy.

MiR-195, miR-196b, miR-181c, miR-21 expression levels and O-6-methylguanine-DNA methyltransferase methylation status are associated with clinical outcome in glioblastoma patients.

Glioblastoma multiforme (GBM) is the most frequently occurring primary malignant brain tumor; patients with GBM often have a very poor prognosis and differing responses to treatment. Therefore, it is very important to find new biomarkers that can predict clinical outcomes and help in treatment decisions. MicroRNAs are small, non-coding RNAs that function as post-transcriptional regulators of gene expression and play a key role in the pathogenesis of GBM. In a group of 38 patients with primary GBM, we analyzed the expression of eight microRNAs (miR-21, miR-128a, miR-181c, miR-195, miR-196a, miR-196b, miR-221, and miR-222). In addition, we examined the methylation status of O-6-methylguanine-DNA methyltransferase (MGMT) promoter by high-resolution melting analysis, as this has been shown to be a predictive marker in GBM. MGMT methylation status correlated with progression-free survival (P = 0.0201; log-rank test) as well as with overall survival (P = 0.0054; log-rank test). MiR-195 (P = 0.0124; log-rank test) and miR-196b (P = 0.0492; log-rank test) positively correlated with overall survival. Evaluation of miR-181c in combination with miR-21 predicted time to progression within 6 months of diagnosis with 92% sensitivity and 81% specificity (P < 0.0001). Our data confirmed that the methylation status of MGMT but also miR-21, miR-181c, miR-195, and miR-196b to be associated with survival of GBM patients. Above all, we suggest that the combination of miR-181c and miR-21 could be a very sensitive and specific test to identify patients at high risk of early progression after surgery.