Microsurgical treatment of symptomatic spinal extradural arachnoid cyst: a consecutive case series of 34 patients and literature review.

PURPOSE: A spinal extradural arachnoid cyst (SEAC) is a rare condition with unclear etiology. Herein, we report a series of symptomatic SEACs to illustrate features of SEACs in adults, surgical management, and outcomes. METHODS: A total of 34 consecutive patients who underwent microsurgical treatment were retrospectively reviewed. Patient characteristics were recorded in each case, including presenting symptoms, imaging findings, neurologic status, a surgical procedure performed and follow-up. RESULTS: There were 19 (56%) male and 15 (44%) female patients, with the ages ranging from 16 to 71 years (average 45 years). The lesions were located in the cervical segment (n = 4, 12%), thoracic segment (n = 6, 18%), thoracolumbar segment (n = 10, 29%) and lumbar segment (n = 14, 41%). Clinical presentations included back pain (n = 18, 53%), sensory deficits (n = 14, 41%), weakness (n = 4, 12%) and gait ataxia (n = 4, 12%), with a mean duration of symptoms of 17 months. The lesion was hypointense with the spinal cord on T1-weighted images and hyperintense on T2-weighted images and showed no homogeneous enhancement after contrast medium injection. Communication between the cyst and subarachnoid space was found in 23 patients and the cyst was resected after fistula ligation. Postoperatively, patients were followed up for an average of 80 months. The patients' symptoms dramatically improved and follow-up radiological images showed a complete disappearance of the cyst in all patients. No recurrence was observed in the dural repair group. CONCLUSION: Patients with symptomatic SEAC present with obvious and persistent symptoms. Complete microsurgical cyst removal with the closure of the dural defect is the standard treatment procedure with good results and a low recurrence rate.

A Novel Six-mRNA Signature Predicts Survival of Patients With Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is a devastating brain tumor and displays divergent clinical outcomes due to its high degree of heterogeneity. Reliable prognostic biomarkers are urgently needed for improving risk stratification and survival prediction. In this study, we analyzed genome-wide mRNA profiles in GBM patients derived from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to identify mRNA-based signatures for GBM prognosis with survival analysis. Univariate Cox regression model was used to evaluate the relationship between the expression of mRNA and the prognosis of patients with GBM. We established a risk score model that consisted of six mRNA (AACS, STEAP1, STEAP2, G6PC3, FKBP9, and LOXL1) by the LASSO regression method. The six-mRNA signature could divide patients into a high-risk and a low-risk group with significantly different survival rates in training and test sets. Multivariate Cox regression analysis confirmed that it was an independent prognostic factor in GBM patients, and it has a superior predictive power as compared with age, IDH mutation status, MGMT, and G-CIMP methylation status. By combining this signature and clinical risk factors, a nomogram can be established to predict 1-, 2-, and 3-year OS in GBM patients with relatively high accuracy.

Transcriptome analysis and prognostic model construction based on splicing profiling in glioblastoma.

Glioblastoma (GBM) is the most aggressive malignant brain tumour, with high morbidity and mortality rates. Currently, there is a lack of systematic and comprehensive analysis on the prognostic significance of alternative splicing (AS) profiling for GBM. The GBM data, including RNA-sequencing, corresponding clinical information and the expression levels of splicing factor genes, were downloaded from The Cancer Genome Atlas and the SpliceAid2 database. The prognostic models were assessed by the least absolute shrinkage and selection operator Cox regression analysis. The correlation network between survival-associated AS events and splicing factors was plotted. Prognostic models were built for every AS event type and performed well for risk stratification in patients with GBM. The final prognostic signature served as an independent prognostic factor [hazard ratio (HR), 4.61; 95% confidence interval (CI), 2.97-7.16; P=9.66×10-12] for several clinical parameters, including age, sex, isocitrate dehydrogenase mutation, O6-methylguanine-DNA methyltransferase promoter methylation and risk score. The HR for risk score with GBM was 1.0063 (95% CI, 1.0024-1.0103). The splicing regulatory network indicated that heat shock protein b-1, protein arginine N-methyltransferase 5, protein FAM50B and endoplasmic reticulum chaperone BiP genes were independent prognostic factors for GBM. The results of the present study support the ongoing effort in developing novel genomic models and providing potentially more effective treatment options for patients with GBM.

Prognostic model and nomogram construction based on autophagy signatures in lower grade glioma.

The median survival time of lower grade glioma (LGG) tumors spans a wide range of 2-10 years and is highly dependent on the molecular characteristics and tumor location. Currently, there is no prognostic predictor for these tumors based on autophagy-related (ATG) genes. A prognostic risk score model based on the most significant seven ATG genes was established for LGG. These seven genes, including GRID2, FOXO1, MYC, PTK6, IKBKE, BIRC5, and TP73, have been screened as potentially therapeutic targets. The Kaplan-Meier survival curve analyses validated that patients with high or low risk scores had significantly different overall survival. Following the multivariate Cox regression and area under the ROC curve (AUC) analysis, a final prognostic model based on age, World Health Organization grade, 1p19q-codeletion status, and ATG risk score was performed as an independent prognostic indicator (training set: p = 4.09E-05, AUC = 0.901; validation set-1: p = .00069, AUC = 0.808; validation set-2: p = .0376, AUC = 0.830). Subsequently, a prognostic nomogram was constructed for individualized survival prediction. The calibration plots showed excellent predict efficiency between probability and actual overall survival. In this study, we provided several potential biomarkers for further developing potentially therapeutic targets of LGG. We also established a prognostic model and nomogram to improve the clinical glioma management and assist individualized survival prediction.

Denoising ghost imaging under a small sampling rate via deep learning for tracking and imaging moving objects.

Ghost imaging (GI) usually requires a large number of samplings, which limit the performance especially when dealing with moving objects. We investigated a deep learning method for GI, and the results show that it can enhance the quality of images with the sampling rate even down to 3.7%. With a convolutional denoising auto-encoder network trained with numerical data, blurry images from few samplings can be denoised. Then those outputs are used to reconstruct both the trajectory and clear image of the moving object via cross-correlation based GI, with the number of required samplings reduced by two-thirds.

miR-29a-5p Regulates the Proliferation, Invasion, and Migration of Gliomas by Targeting DHRS4.

Gliomas are the most common malignant primary brain tumors in adults and exhibit a spectrum of aberrantly aggressive phenotypes. MicroRNAs (miRNAs) play a regulatory role in various cancers, including gliomas; however, their specific roles and mechanisms have not been fully investigated. Studies have indicated that miR-29a is a tumor-suppressive miRNA, but the data are limited. In this study, we investigated the role of miR-29a-5p in glioma and further explored its underlying mechanisms. On the basis of bioinformatics, dehydrogenase/reductase 4 (DHRS4) was considered a potential target of miR-29a-5p and was also found to be highly expressed in gliomas in our experiments. Moreover, with a luciferase reporter assay, DHRS4 was found to be a target gene of miR-29a-5p and to be correlated with glioma proliferation, invasion, and migration in our in vivo and in vitro experiments. Simultaneously, we observed that the knockdown of DHRS4 rescued the downregulation of glioma proliferation, invasion, and migration caused by treatment with a mir-29a-5p inhibitor. The present findings demonstrate that miR-29a-5p suppresses cell proliferation, invasion, and migration by targeting DHRS4, and DHRS4 may be a potential new oncogene and prognostic factor in gliomas.

LINC00909 promotes tumor progression in human glioma through regulation of miR-194/MUC1-C axis.

Long non-coding RNAs (lncRNAs) play important roles in tumor progression. Whereas the roles and underlying mechanisms of LINC00909 (a newly discovered lncRNA) are still unclear in glioma progression. In the present study, we identified that LINC00909 expression was significantly elevated in glioma tissues and cell lines. High LINC00909 expression was associated with advanced WHO grade, high Karnofsky Performance Score (KPS), and poor prognosis in patients with glioma. Function assays showed that LINC00909 depletion inhibited glioma cells proliferation, invasion in vitro and reduced tumor growth in vivo. In the mechanism, we found that LINC00909 could act as a ceRNA to interact with miR-194 and thereby up-regulate the expression of MUC1-C, thus promoting the proliferation and invasion of glioma cells. Collectively, these data demonstrated that LINC00909/miR-194/MUC1-C axis regulated glioma progression and might act as a novel therapeutic target.

Overexpression of ubiquitin specific proteases 44 promotes the malignancy of glioma by stabilizing tumor-promoter securin.

Ubiquitin specific peptidase 44 (USP44) has been identified as an important component of spindle assemble checkpoint (SAC) to prevent the formation of aneuploidy. However, recent study raised a controversy about the effect of USP44 in tumor. Here, we first confirmed the intranuclear localization of USP44 by testing several specific antibodies to recognize endogenous USP44. Then, data from IHC and qRT-PCR assay indicated that the high expression of USP44 existed in high-grade glioma tissues and signified a poor prognosis. Knockdown of USP44 inhibited proliferation, migration and invasion, induced apoptosis, and arrested cell cycle in G2/M phase in the established glioma cell lines. Down-regulation of oncoprotein securin was detected in USP44 deficient cells, and the interaction of endogenous USP44 and securin was confirmed by immunoprecipitation in U251MG cells, which indicated that securin was a substrate of USP44, and might be stabilized by USP44. In vivo, knockdown of USP44 inhibited the tumorigenicity of U87MG cells significantly. Consequently, our findings suggested that overexpression of USP44 could enhance the malignancy of glioma via securin. USP44 might serve as a predictive biomarker, and the USP44-securin pathway might provide a new therapeutic strategy for the treatment of glioma.

RIZ1 negatively regulates ubiquitin-conjugating enzyme E2C/UbcH10 via targeting c-Myc in meningioma.

RIZ1 has been considered as an important tumor suppressor gene. Our previous studies have already demonstrated that the expression of RIZ1 is closely related to the occurrence and development of meningioma. In addition, we also found that the expression of UbcH10 was related to the pathologic grade of meningioma which also affected the prognosis of these patients. However, we are lack of the understanding of the effect of UbcH10 on cell proliferation, cell apoptosis, cell cycle and other functions in meningioma cells. Besides, the regulation mechanism between RIZ1 and UbcH10 still remains unclear. In this study, we attempted to demonstrated that UbcH10 was a downstream target of RIZ1 and reported that UbcH10 silencing might negatively regulate cell proliferation, migration, invasion and promote apoptosis, which is similar to the cell phenotype that of over expressed RIZ1. Mechanistically, we proved that UbcH10 was a c-Myc target gene and that RIZ1 regulated UbcH10 expression in a c-Myc-dependent manner. For the first time, our study demonstrated that UbcH10 played a key role in the proliferation, metastasis and apoptosis of primary human malignant meningioma cells. In addition, the mechanism of RIZ1 regulating UbcH10 is also clear. Our study can also provide a potential target and new idea for the follow-up molecular intervention in clinical malignant meningiomas.

Tissue thioredoxin-interacting protein expression predicted recurrence in patients with meningiomas.

BACKGROUND: The redox regulatory protein, thioredoxin-interacting protein (TXNIP), has been confirmed as an important tumor suppressor gene in various types of human cancers. In previous studies, we found that overexpression of tumor suppressor gene RIZ1 in meningiomas can significantly improve the expression of TXNIP by microarray data analysis. Therefore, we hypothesized that TXNIP was associated with the initiation and progression of meningiomas. METHODS: First, we evaluated the expression of TXNIP and Ki-67 in meningioma tissues from 65 patients using immunohistochemistry. We also analyzed the correlation between TXNIP immunoreactivity and clinicopathological features, as well as patient prognostic factors. RESULTS: According to immunohistochemistry results, high-grade meningioma tissues had significantly lower expression of TXNIP than benign meningioma tissues (29.31 ± 18.70 vs 74.61 ± 7.51, P < 0.0001). TXNIP and Ki67 were negatively correlated (P < 0.0001). Moreover, the expression of TXNIP was higher in nonrecurrent high-grade meningiomas (P < 0.05). In addition, Kaplan-Meier analysis indicated that expression of TXNIP and Ki-67 was related to recurrence-free time. Multivariate Cox analysis showed that TXNIP expression level was the only independent predictor for meningioma prognosis. CONCLUSION: Our results demonstrated that high expression of TXNIP indicates a lower pathological grade of meningnioma, and is also associated with longer recurrence-free time. Therefore, TXNIP could be regarded as a potential molecular marker to predict recurrence in patients with meningiomas.

Differential Expression of Circular RNAs in Glioblastoma Multiforme and Its Correlation with Prognosis.

OBJECTIVE: The present study aimed to explore the expression profiles of circular RNAs (circRNAs) in glioblastoma multiforme (GBM) in an attempt to identify potential core genes in the pathogenesis of this tumor. METHODS: Differentially expressed circRNAs were screened between tumor tissues from five GBM patients and five normal brain samples using Illumina Hiseq. Bioinformatics analysis was used to analyze their potential function. CircBRAF was further detected in different WHO grades glioma tissues and normal brain tissues. Kaplan-Meier curves and multivariate Cox's analysis were used to analyze the association between circBRAF expression level and prognosis of glioma patients. RESULTS: A total of 1411 differentially expressed circRNAs were identified in GBM patients including 206 upregulated circRNAs and 1205 downregulated circRNAs. Differential expression of circRNAs was closely associated with the biological process and molecular function. The downregulated circRNAs were mainly associated with ErbB and Neurotrophin signaling pathways. Moreover, the expression level of circBRAF in normal brain tissues was significantly higher than that in glioma tissues (P<.001). CircBRAF was significantly lower in glioma patients with high pathological grade (WHO III & IV) than those with low grade (WHO I & II) (P<.001). Cox analysis revealed that high circBRAF expression was an independent biomarker for predicting good progression-free survival and overall survival in glioma patients (HR=0.413, 95% CI 0.201-0.849; HR=0.299, 95% CI 0.135-0.661; respectively). CONCLUSION: The present study identified a profile of dysregulated circRNAs in GBM. Bioinformatics analysis showed that dysregulated circRNAs might be associated with tumorigenesis and development of GBM. In addition, circBRAF could severe as a biomarker for predicting pathological grade and prognosis in glioma patients.

Down-regulation of long non-coding RNA FOXD3 antisense RNA 1 (FOXD3-AS1) inhibits cell proliferation, migration, and invasion in malignant glioma cells.

Growing evidence indicates that long non-coding RNAs (lncRNAs) play key roles in cancer initiation and progression. However, little is known about the therapeutic significance of lncRNAs in glioma. In this study, we explored the tumorigenic role of a classical lncRNA, FOXD3 antisense RNA 1 (FOXD3-AS1) in glioma. Systemic analysis of the patient specimens and clinical data showed that FOXD3-AS1 was markedly up-regulated in high-grade glioma tissues (WHO grade III-IV) compared with that in low-grade glioma (WHO grade I-II) and normal brain tissues (both P<0.01), and patients with low FOXD3-AS1 expression had grater survival probability. Multivariate regression analysis showed that increased FOXD3-AS1 expression was a significant independent indicator of poor prognosis in glioma patients (P=0.034). To understand the tumorigenic mechanism of FOXD3-AS1, the expression pattern and functional role of FOXD3-AS1 in glioma were detected using real-time PCR and Smart Silencer-mediated knockdown study. In related cell biological assays, we discovered that FOXD3-AS1 knockdown significantly inhibited cell proliferation, induced cell cycle S-phase arrest, and impaired cell migration and invasion in malignant glioma cells. As expected, we also found that the expression of FOXD3-AS1 was positively correlated with FOXD3 mRNA. Knockdown of FOXD3-AS1 reduced the protein level of FOXD3 in cultured U251 and A172 cell lines. These results suggest that FOXD3-AS1 is an oncogenic lncRNA, which may promote the occurrence and development of glioma through transcriptional regulation of FOXD3.

Anti-tumor activity of phenoxybenzamine hydrochloride on malignant glioma cells.

Phenoxybenzamine hydrochloride (PHEN) is a selective antagonist of both α-adrenoceptor and calmodulin that exhibits anticancer properties. The aim of this study was to explore the anti-tumor function of PHEN in glioma. Cell proliferation assay was used to assess glioma cell growth. Migration and invasion capacity of glioma cells was monitored by wound-healing and transwell assay, respectively. Neurosphere formation test was adopted for the tumorigenesis of glioma cells, which was also confirmed by soft agar cloning formation test in vitro and a nude mouse model in vivo. Finally, we explored the potential pathway utilized by PHEN using Western blot and immunofluoresce staining. PHEN exhibited a significant inhibitory effect on the proliferation of both U251 and U87MG glioma cell lines in a positive dose-dependent manner. PHEN apparently attenuated the malignancy of glioma in terms of migration and invasion and also suppressed the tumorigenic capacity both in vitro and in vivo. Mechanism study showed that PHEN promoted tumor suppression by inhibiting the TrkB-Akt pathway. The results of the present study demonstrated that PHEN suppressed the proliferation, migration, invasion, and tumorigenesis of glioma cells, induced LINGO-1 expression, and inhibited the TrkB-Akt pathway, which may prove to be the mechanisms underlying the anti-tumor effect of PHEN on glioma cells.