Survival Rate Of Glioma Patients Research Articles

Complement factor H is an ICOS ligand modulating Tregs in the glioma microenvironment.

The survival rate of glioma patients has not significantly increased in recent years despite aggressive treatment and advances in immunotherapy. The limited response to treatments is partially attributed to the immunosuppressive tumor microenvironment, where regulatory T cells (Tregs) play a pivotal role in immunological tolerance. In this study, we investigated the impact of complement factor H (FH) on Tregs within the glioma microenvironment and found that FH is an ICOS ligand. The binding of FH to this immune checkpoint molecule promoted the survival and function of Tregs and induced the secretion of TGF-beta (TGF-β) and IL-10, while also suppressing T-cell proliferation. We further demonstrated that cancer cells in human and mouse gliomas directly produce FH. Database investigations revealed that upregulation of FH expression was associated with the presence of Tregs and correlated with worse prognosis for glioma patients. We confirmed the effect of FH on glioma development in a mouse model, where FH knockdown was associated with decrease in number of ICOS+ Tregs and demonstrated a tendency of prolonged survival (p=0.064). Since the accumulation of Tregs represents a promising prognostic and therapeutic target, evaluating FH expression should be considered when assessing the effectiveness of and resistance to immunotherapies against glioma.

An online survival predictor in glioma patients using machine learning based on WHO CNS5 data.

The World Health Organization (WHO) CNS5 classification system highlights the significance of molecular biomarkers in providing meaningful prognostic and therapeutic information for gliomas. However, predicting individual patient survival remains challenging due to the lack of integrated quantitative assessment tools. In this study, we aimed to design a WHO CNS5-related risk signature to predict the overall survival (OS) rate of glioma patients using machine learning algorithms. We extracted data from patients who underwent an operation for histopathologically confirmed glioma from our hospital database (2011-2022) and split them into a training and hold-out test set in a 7/3 ratio. We used biological markers related to WHO CNS5, clinical data (age, sex, and WHO grade), and prognosis follow-up information to identify prognostic factors and construct a predictive dynamic nomograph to predict the survival rate of glioma patients using 4 kinds machine learning algorithms (RF, SVM, XGB, and GLM). A total of 198 patients with complete WHO5 molecular data and follow-up information were included in the study. The median OS time of all patients was 29.77 [95% confidence interval (CI): 21.19-38.34] months. Age, FGFR2, IDH1, CDK4, CDK6, KIT, and CDKN2A were considered vital indicators related to the prognosis and OS time of glioma. To better predict the prognosis of glioma patients, we constructed a WHO5-related risk signature and nomogram. The AUC values of the ROC curves of the nomogram for predicting the 1, 3, and 5-year OS were 0.849, 0.835, and 0.821 in training set, and, 0.844, 0.943, and 0.959 in validation set. The calibration plot confirmed the reliability of the nomogram, and the c-index was 0.742 in training set and 0.775 in validation set. Additionally, our nomogram showed a superior net benefit across a broader scale of threshold probabilities in decision curve analysis. Therefore, we selected it as the backend for the online survival prediction tool (Glioma Survival Calculator, https://who5pumch.shinyapps.io/DynNomapp/), which can calculate the survival probability for a specific time of the patients. An online prognosis predictor based on WHO5-related biomarkers was constructed. This therapeutically promising tool may increase the precision of forecast therapy outcomes and assess prognosis.

Interferon gamma-related gene signature based on anti-tumor immunity predicts glioma patient prognosis.

Background: Glioma is the most common primary tumor of the central nervous system. The conventional glioma treatment strategies include surgical excision and chemo- and radiation-therapy. Interferon Gamma (IFN-γ) is a soluble dimer cytokine involved in immune escape of gliomas. In this study, we sought to identify IFN-γ-related genes to construct a glioma prognostic model to guide its clinical treatment. Methods: RNA sequences and clinicopathological data were downloaded from The Cancer Genome Atlas (TCGA) and the China Glioma Genome Atlas (CGGA). Using univariate Cox analysis and the Least Absolute Shrinkage and Selection Operator (LASSO) regression algorithm, IFN-γ-related prognostic genes were selected to construct a risk scoring model, and analyze its correlation with the clinical features. A high-precision nomogram was drawn to predict prognosis, and its performance was evaluated using calibration curve. Finally, immune cell infiltration and immune checkpoint molecule expression were analyzed to explore the tumor microenvironment characteristics associated with the risk scoring model. Results: Four out of 198 IFN-γ-related genes were selected to construct a risk score model with good predictive performance. The expression of four IFN-γ-related genes in glioma tissues was significantly increased compared to normal brain tissue (p < 0.001). Based on ROC analysis, the risk score model accurately predicted the overall survival rate of glioma patients at 1 year (AUC: The Cancer Genome Atlas 0.89, CGGA 0.59), 3years (AUC: TCGA 0.89, CGGA 0.68), and 5years (AUC: TCGA 0.88, CGGA 0.70). Kaplan-Meier analysis showed that the overall survival rate of the high-risk group was significantly lower than that of the low-risk group (p < 0.0001). Moreover, high-risk scores were associated with wild-type IDH1, wild-type ATRX, and 1P/19Q non-co-deletion. The nomogram predicted the survival rate of glioma patients based on the risk score and multiple clinicopathological factors such as age, sex, pathological grade, and IDH Status, among others. Risk score and infiltrating immune cells including CD8 T-cell, resting CD4 memory T-cell, regulatory T-cell (Tregs), M2 macrophages, resting NK cells, activated mast cells, and neutrophils were positively correlated (p < 0.05). In addition, risk scores closely associated with expression of immune checkpoint molecules such as PD-1, PD-L1, CTLA-4, LAG-3, TIM-3, TIGIT, CD48, CD226, and CD96. Conclusion: Our risk score model reveals that IFN-γ -associated genes are an independent prognostic factor for predicting overall survival in glioma, which is closely associated with immune cell infiltration and immune checkpoint molecule expression. This model will be helpful in predicting the effectiveness of immunotherapy and survival rate in patients with glioma.

An integrative bioinformatics investigation and experimental validation of critically involved genes in high-grade gliomas

BackgroundLack of knowledge around underlying mechanisms of gliomas mandates intense research efforts to improve the disease outcomes. Identification of high-grade gliomas pathogenesis which is known for poor prognosis and low survival is of particular importance. Distinguishing the differentially expressed genes is one of the core approaches to clarify the causative factors.MethodsMicroarray datasets of the treatment-naïve gliomas were provided from the Gene Expression Omnibus considering the similar platform and batch effect removal. Interacting recovery of the top differentially expressed genes was performed on the STRING and Cytoscape platforms. Kaplan–Meier analysis was piloted using RNA sequencing data and the survival rate of glioma patients was checked considering selected genes. To validate the bioinformatics results, the gene expression was elucidated by real-time RT-qPCR in a series of low and high-grade fresh tumor samples.ResultsWe identified 323 up-regulated and 253 down-regulated genes. The top 20 network analysis indicated that PTX3, TIMP1, CHI3L1, LTF and IGFBP3 comprise a crucial role in gliomas progression. The survival was inversely linked to the levels of all selected genes. Further analysis of RNA sequencing data indicated a significant increase in all five genes in high-grade tumors. Among them, PTX3, TIMP1 and LTF did not show any change in low-grade versus controls. Real-time RT-qPCR confirmed the in-silico results and revealed significantly higher expression of selected genes in high-grade samples compared to low-grade.ConclusionsOur results highlighted the role of PTX3 and TIMP1 which were previously considered in glioma tumorigenesis as well as LTF as a new potential biomarker.

Ferroptosis in Glioma Immune Microenvironment: Opportunity and Challenge.

Glioma is the most common intracranial malignant tumor in adults and the 5-year survival rate of glioma patients is extremely poor, even in patients who received Stupp treatment after diagnosis and this forces us to explore more efficient clinical strategies. At this time, immunotherapy shows great potential in a variety of tumor clinical treatments, however, its clinical effect in glioma is limited because of tumor immune privilege which was induced by the glioma immunosuppressive microenvironment, so remodeling the immunosuppressive microenvironment is a practical way to eliminate glioma immunotherapy resistance. Recently, increasing studies have confirmed that ferroptosis, a new form of cell death, plays an important role in tumor progression and immune microenvironment and the crosstalk between ferroptosis and tumor immune microenvironment attracts much attention. This work summarizes the progress studies of ferroptosis in the glioma immune microenvironment.

Neuroplasticity of Glioma Patients: Brain Structure and Topological Network.

Glioma is the most common primary malignant brain tumor in adults. It accounts for about 75% of such tumors and occurs more commonly in men. The incidence rate has been increasing in the past 30 years. Moreover, the 5-year overall survival rate of glioma patients is < 35%. Different locations, grades, and molecular characteristics of gliomas can lead to different behavioral deficits and prognosis, which are closely related to patients' quality of life and associated with neuroplasticity. Some advanced magnetic resonance imaging (MRI) technologies can explore the neuroplasticity of structural, topological, biochemical metabolism, and related mechanisms, which may contribute to the improvement of prognosis and function in glioma patients. In this review, we summarized the studies conducted on structural and topological plasticity of glioma patients through different MRI technologies and discussed future research directions. Previous studies have found that glioma itself and related functional impairments can lead to structural and topological plasticity using multimodal MRI. However, neuroplasticity caused by highly heterogeneous gliomas is not fully understood, and should be further explored through multimodal MRI. In addition, the individualized prediction of functional prognosis of glioma patients from the functional level based on machine learning (ML) is promising. These approaches and the introduction of ML can further shed light on the neuroplasticity and related mechanism of the brain, which will be helpful for management of glioma patients.

Decreased Expression of PACSIN1 in Brain Glioma Samples Predicts Poor Prognosis.

Gliomas are the most severe brain tumours with a poor prognosis. Although surgery, postoperative radiotherapy and chemotherapy can improve the survival rate of glioma patients, the prognosis of most glioma patients is still poor. In recent years, the influence of gene-targeted therapy on gliomas has been gradually discovered, and intervening the occurrence and development of brain gliomas from the perspective of the gene will significantly improve treatment prognosis. Protein Kinase C and Casein Kinase Substrate in Neurons 1 (PACSIN1) is a member of the conserved peripheral membrane protein family in eukaryotes. Improper expression of PACSIN1 can lead to neurological diseases such as Huntington’s disease and schizophrenia. However, its relationship with tumours or even gliomas has not been explored. The study aims to explore PACSIN1 as a prognostic factor that can predict overall survival (OS) for gliomas. We collected the data from CGGA, TCGA, GEO databases and the pathological glioma tissue specimens from 15 clinical glioma patients surgically resected. The differential expression of PACSIN1 in various clinical indicators, the genes related to PACSIN1 expression, the prognostic value of PACSIN1 and the functional annotations and pathway analysis of differently expressed genes (DEGs) were analysed. The results revealed that PACSIN1 had low expression levels in grade IV, IDH1 wild-type and 1p/19q non-codel group gliomas, and PACSIN1 was considered a mesenchymal molecular subtype marker. PACSIN1 expression is positively correlated with OS in all gliomas and it was found that PACSIN1 influenced the occurrence and development of gliomas through synaptic transmission. The PACSIN1 expression is negatively correlated with the malignant degree of gliomas and positively associated with the OS, indicating that PACSIN1 would play an essential role in the occurrence and development of gliomas and might be a potential new biomarker and targeted therapy site for gliomas.

Multiparametric MRI Features Predict the SYP Gene Expression in Low-Grade Glioma Patients: A Machine Learning-Based Radiomics Analysis.

PurposeSynaptophysin (SYP) gene expression levels correlate with the survival rate of glioma patients. This study aimed to explore the feasibility of applying a multiparametric magnetic resonance imaging (MRI) radiomics model composed of a convolutional neural network to predict the SYP gene expression in patients with glioma.MethodUsing the TCGA database, we examined 614 patients diagnosed with glioma. First, the relationship between the SYP gene expression level and outcome of survival rate was investigated using partial correlation analysis. Then, 7266 patches were extracted from each of the 108 low-grade glioma patients who had available multiparametric MRI scans, which included preoperative T1-weighted images (T1WI), T2-weighted images (T2WI), and contrast-enhanced T1WI images in the TCIA database. Finally, a radiomics features-based model was built using a convolutional neural network (ConvNet), which can perform autonomous learning classification using a ROC curve, accuracy, recall rate, sensitivity, and specificity as evaluation indicators.ResultsThe expression level of SYP decreased with the increase in the tumor grade. With regard to grade II, grade III, and general patients, those with higher SYP expression levels had better survival rates. However, the SYP expression level did not show any significant association with the outcome in Level IV patients.ConclusionOur multiparametric MRI radiomics model constructed using ConvNet showed good performance in predicting the SYP gene expression level and prognosis in low-grade glioma patients.

TRIB3 confers glioma cell stemness via interacting with β-catenin.

Here, we aim to explore whether tribbles pseudokinase 3 (TRIB3) enhances glioma cell stemness. TRIB3 was overexpressed in glioma tissues and cell-formed spheres, positively correlated with the size and grade. Additionally, TRIB3 expression displayed a negative correlation with the overall survival rate of glioma patients. Moreover, TRIB3 knockdown reduced the stemness of nonadherent spheres, evident by the decreased sphere-forming ability, stemness master expression, and ALDH1 activity, while TRIB3 overexpression enhanced the stemness of adherent cells, which was rescued by β-catenin knockdown. Mechanistically, TRIB3 activated β-catenin signaling via physically interacting with β-catenin. This study suggests that the TRIB3-β-catenin interaction is responsible for glioma cell stemness.

Cyclovirobuxine D inhibits cell proliferation and migration and induces apoptosis in human glioblastoma multiforme and low‑grade glioma.

Gliomas are the most common neoplasm of the human central nervous system. Glioblastoma multiforme (GBM) is one of the most serious types of gliomas. Although considerable progress has been made in the development of cancer therapeutic agents, several antineoplastic drugs fail to penetrate the blood-brain barrier (BBB), resulting in a low survival rate of glioma patients. Recent studies have revealed that the traditional Chinese medicine Buxus microphylla contains the main active component Cyclovirobuxine D (CVB-D), which can cross the BBB with a novel delivery system. However, it remains unclear whether CVB-D exerts anticancer effects against GBM and low-grade glioma (LGG). The aim of the present study was to explore the feasibility of CVB-D as a new effective agent in the treatment of GBM and LGG. The ability of CVB-D to inhibit GBM and LGG cell proliferation was detected by CCK8 assay. Flow cytometry was used to detect cell cycle progression and apoptosis induction by Annexin V-FITC/PI assay. The expression levels of the apoptosis-associated proteins, namely cleaved caspase-3 and Bax/Bcl-2, were detected by western blot analysis. The mitochondrial membrane potential (ΔΨm) was detected by Rh123 dyed fluorescence micrograph. Hoechst staining was used to observe the morphological characteristics of the apoptotic cells. The scratch test was used to evaluate the migration of GBM and LGG cells. The results indicated that CVB-D reduced cell viability of T98G and Hs683 cells. Flow cytometry demonstrated that CVB-D-treated cells were arrested at the S phase of their cell cycle. The expression levels of the apoptosis-associated proteins were increased in CVB-D-treated cells. Rh123 and Hoechst staining indicated morphological changes and mitochondrial membrane potential changes of the cells undergoing apoptosis. The data confirmed that CVB-D inhibited cell proliferation by arresting the cell cycle of GBM and LLG cells and that it promoted the induction of cell apoptosis by altering the mitochondrial membrane potential. The findings of the present study indicate the potential value of CVB-D in the treatment of glioma.

Identification of Mir-9 in Glioma Diagnosis and Prognosis.

Mir-9 was recognized as a potential tumor suppressor gene or oncogene in varies of diseases; however, its roles in glioma have not been investigated. Our study was to identify the mRNA expression of mir-9 gene in glioma and correlate abnormal versions of microRNAs with clinicopathological features and investigate the impact of mir-9 in glioma prognosis. Seventy-one glioma samples, which included 22 grade II, 24 grade III, and 25 glioblastoma tumors of previously untreated patients who underwent surgical excision at Qing Hai Province People's Hospital from 2011 to 2014, were included. In addition, 2 epilepsy patients with normal brain tissue were included as a control group. The expression of mir-9 was examined by RT-PCR in formalin-fixed paraffin embedded primary tissue specimens. The clinicopathologic features, the survival rate of glioma patients were also discussed. The RNA expression of mir-9 and glioma prognosis was evaluated using a Chi-square test, Cox regression model, and GraphPad Prism survival curve analysis. There were 16, 20, 21 cases which showed high expression of mir-9 in grade II and III gliomas and glio-blastoma, 16/22 (72.7%), 20/24 (83.3%), 21/25 (84.0%), respectively. The expression of mir-9 was correlated with the grade of glioma. The mir-9 RNA expression in glioblastoma were higher than grade II and III gliomas (p < 0.05). The higher the grade, the higher the expression, and the difference was significant (p < 0.05), while it was not correlated with patient nationality, gender, or location (p > 0.05). Univariate analysis determined that high expression of mir-9, grade, chemotherapy, radiation therapy, and patient onset age were associated with glioma patient prognosis (p < 0.05). The expression of mir-9 plays a role in glioma progression, and may be used as a prognostic marker in glioma.

Up‑regulation of lncRNA PXN-AS1-L is associated with unfavorable prognosis in patients suffering from glioma.

Growing evidence has proved that long noncoding RNAs (lncRNAs) act as novel regulators in the progression of various tumors by modulating miRNAs and tumor-related genes. However, the potential function of lncRNA PXN-AS1-L (PXN-AS1-L) in glioma remains unknown. Hence, we aimed to determine whether PXN-AS1-L was dysregulated in glioma and further preliminarily explored its prognostic value in glioma patients. RT-PCR was used for the assessment of PXN-AS1-L levels in glioma tissue and matched normal tissues from our hospital. Chi-square test was applied to explore the possible association between PXN-AS1-L expressions and clinical factors. Kaplan-Meier survival analysis was carried out to determine the influence of PXN-AS1-L expressions on the survival rate of glioma patients. Survival data were further evaluated through univariate and multivariate analyses. PXN-AS1-L levels were differentially upregulated in glioma specimens compared with paired non-tumor specimens. Higher levels of PXN-AS1-L in glioma were observed to be positively associated with WHO grade (p = 0.019), KPS (p = 0.008)and tumor recurrence (p = 0.019). Survival assays revealed that glioma patients with higher PXN-AS1-L expressions had worse overall survival rates. In multivariate analysis, upregulation of PXN-AS1-L expressions (Risk ratio = 2.663, 1.218-4.532, p = 0.014) in glioma tissues was confirmed to be an independent prognostic factor of overall survival in patients. We firstly suggested that PXN-AS1-L was overexpressed in glioma, and could be used as a novel marker of unfavorable outcome in glioma patients.

Evolution of Nucleic Acid Aptamers Capable of Specifically Targeting Glioma Stem Cells via Cell-SELEX.

Glioma stem cells (GSCs), a particular group of cells from gliomas, are capable of infinite proliferation and differentiation. Recent studies have shown that GSCs may be the root of tumor recurrence, metastasis, and resistance. Early detection and targeted therapy of GSCs may significantly improve the survival rate of glioma patients. Therefore, molecular ligands capable of selectively recognizing GCSs are of great importance. The objective of this study is to generate DNA aptamers for selective identification of the molecular signature of GSCs using cell-based Systematic Evolution of Ligands by EXponential enrichment (cell-SELEX). GSCs were used as the positive selection target, while U87 cells were used in negative cycles for removal of DNA molecules binding to common glioma cell lines. Finally, we successfully identified one aptamer named W5-7 with a Kd value of 4.9 ± 1.4 nM. The sequence of the aptamer was further optimized, and its binding target was identified as a membrane protein. The aptamer W5-7 was stable in cerebral spinal fluid over 36 h and could also effectively detect glioma stem cells in cerebral spinal fluid samples. With its superb targeting properties and functional versatility, W5-7 holds great potential for use as a molecular probe for detecting and isolating GSCs.

Long non‐coding RNA HCG11 suppresses the growth of glioma by cooperating with the miR‐4425/MTA3 axis

Glioma is a type of malignant tumor that occurs in the central nervous system of adults. Long non-coding RNAs (lncRNAs) that potentially participate in the initiation and progression of glioma have been widely reported. As a now-found lncRNA, HLA complex group 11 (HCG11) has not yet been studied in glioma. The present study aimed to determine the role of HCG11 in the tumorigenesis of glioma. A quantitative real-time polymerase chain reaction assay was performed to examine the expression pattern of HCG11 in 84 glioma tissues and cell lines. The overall survival rate of glioma patients with a high or low level of HCG11 or metastasis-associated 1 family member 3 (MTA3) was analyzed by Kaplan-Meier analysis. The effect of HCG11 on glioma cell growth was determined by in vitro and in vivo experiments. MicroRNAs (miRNAs) that potentially interact with HCG11 were searched and determined by bioinformatics analysis and a luciferase reporter assay. Similarly, the target of miRNA-4425 was identified. Finally, rescue assays were conducted to determine the bio-function of the competing endogenous RNA pathway. HCG11 was downregulated in 84 pairs of glioma tissues and cell lines. Moreover, a low level of HCG11 indicted the lower overall survival rate of glioma patients. Regarding the mechanism, HCG11 was abundant in the cytoplasm of glioma cells and interacted with miR-4425 to release the expression of MTA3. miR-4425 and MTA3 participated in HCG11-mediated glioma growth. LncRNA HCG11 suppresses the growth of glioma by cooperating with the miR-4425/MTA3 axis.

LncRNA CASC7 inhibits the progression of glioma via regulating Wnt/β-catenin signaling pathway

Increasing evidence reveal the important role of long non-coding RNAs (lncRNAs) in the initiation and progression of glioma. However, the role of lncRNA cancer susceptibility candidate 7 (CASC7) in glioma is largely unknown. At first, the expression level of CASC7 was tested in glioma tissues and cell lines by using qRT-PCR. We applied Kaplan-Meier method to analyze the correlation between the expression level between CASC7 expression and the overall survival rate of glioma patients. We found that CASC7 was downregulated in glioma tissues and cell liens and predicted poor prognosis for patients with glioma. To determine the involvement of CASC7 in the biological processes of glioma, we conducted gain or loss-of function assays in two glioma patients. We found that CASC7 suppressed glioma cell proliferation and induced glioma cell apoptosis. Mechanistically, the expression level of CASC7 was negatively correlated with the expression levels of core factors of Wnt/β-catenin signaling pathway in glioma cells. Moreover, TOP flash luciferase activity further revealed the negative effect of CASC7 on the activity of Wnt/β-catenin signaling pathway. Finally, rescue assays were carried out to determine that Wnt/β-catenin signaling pathway involved in CASC7-mediated glioma progression. Taken together, all research findings suggested that CASC7 inhibited the progression of glioma via regulating Wnt/β-catenin signaling pathway.

GBP3 promotes glioma cell proliferation via SQSTM1/p62-ERK1/2 axis

Guanylate binding proteins (GBPs) are interferon-inducible large GTPases and play a crucial role in cell-autonomous immunity. However, the biology function of GBPs in cancer remains elusive. GBP3 is specifically expressed in adult brain. Here we show that GBP3 is highly elevated in human glioma tumors and glioma cell lines. Overexpression of GBP3 dramatically increased glioma cell proliferation whereas silencing GBP3 by RNA interference produced opposite effects. We further showed that GBP3 expression was able to induce sequestosome-1(SQSTM1, also named p62) expression and activate extracellular signal-regulated kinase (ERK1/2). The SQSTM1-ERK1/2 signaling cascade was essential for GBP3-promoted cell growth because depletion of SQSTM1 markedly reduced the phosphorylated ERK1/2 levels and GBP3-mediated cell growth, and inhibition of mitogen-activated protein kinase/ERK kinase abolished GBP3-induced glioma cell proliferation. Consistently, GBP3 overexpression significantly promoted glioma tumor growth in vivo and its expression was inversely correlated with the survival rate of glioma patients. Taken together, these results for the first time suggest that GBP3 contributes to the proliferation of glioma cells via regulating SQSTM1-ERK1/2 pathway, and GBP3 might represent as a new potential therapeutic target against glioma.

MicroRNA-211 expression is down-regulated and associated with poor prognosis in human glioma.

Accumulating evidence has supported the role of microRNAs in the initiation and development of malignant tumors. MicroRNA-211 (miR-211), which was reported to involve in diverse physiological activities in several cancers, was investigated for its expression in human glioma and adjacent normal brain tissues, as well as its correlation with patient prognosis. Glioma tissues and adjacent normal brain tissues were obtained from 82 patients who underwent surgical resection, and quantitative real-time polymerase chain reaction was performed to assess the expression level of miR-211. Here, we found that miR-211 was significantly decreased in glioma tissues compared with adjacent normal brain tissues (glioma, 3.52 ± 0.14 vs. normal, 4.96 ± 0.17, p < 0.001), and inversely associated with ascending WHO classification (grade III-IV, 3.16 ± 0.21 vs. grade I-II, 4.22 ± 0.26, p < 0.001). Then, the correlation of miR-211 with clinicopathological factors was investigated by Pearson's Chi square test, indicating that miR-211 might be a potential biomarker to predict the malignant status of glioma. Further, Kaplan-Meier curves with log-rank analysis were carried out to determine the relationship between miR-211 expression level and the overall survival rate of glioma patients. Our data showed that there was a close correlation between down-regulated miR-211 and shorter survival time in 82 patients (p = 0.026). Finally, the multivariate Cox regression analysis indicated that WHO grade (HR = 2.437, 95% CI 1.251-4.966, p = 0.007), KPS (HR = 2.215, 95% CI 1.168-4.259, p = 0.016), and miR-211 expression level (HR = 3.614, 95% CI 2.152-6.748, p < 0.001) were considered as independent risk factors for glioma prognosis. These results suggested that lower miR-211 expression might be a marker for poor prognosis of glioma patients.

Ectopic High Expression of E2-EPF Ubiquitin Carrier Protein Indicates a More Unfavorable Prognosis in Brain Glioma.

Ubiquitination of proteins meant for elimination is a primary method of eukaryotic cellular protein degradation. The ubiquitin carrier protein E2-EPF is a key degradation enzyme that is highly expressed in many tumors. However, its expression and prognostic significance in brain glioma are still unclear. The aim of this study was to reveal how the level of E2-EPF relates to prognosis in brain glioma. Thirty low-grade and 30 high-grade brain glioma samples were divided into two tissue microarrays each. Levels of E2-EPF protein were examined by immunohistochemistry and immunofluorescence. Quantitative real-time polymerase chain reaction was used to analyze the level of E2-EPF in 60 glioma and 3 normal brain tissue samples. The relationship between E2-EPF levels and prognosis was analyzed by Kaplan-Meier survival curves. E2-EPF levels were low in normal brain tissue samples but high in glioma nuclei. E2-EPF levels gradually increased as glioma grade increased (p < 0.05). Ectopic E2-EPF levels in high-grade glioma were significantly higher than in low-grade glioma (p < 0.01). The 5-year survival rate of glioma patients with high E2-EPF levels was shorter than in patients with low expression (p < 0.05). Furthermore, the 5-year survival rate of patients with ectopic E2-EPF was significantly shorter than patients with only nuclear E2-EPF (p < 0.01). These results suggest that higher E2-EPF levels, especially ectopic, are associated with higher grade glioma and shorter survival. E2-EPF levels may play a key role in predicting the prognosis for patients with brain glioma.

Terahertz reflectometry imaging for low and high grade gliomas.

Gross total resection (GTR) of glioma is critical for improving the survival rate of glioma patients. One of the greatest challenges for achieving GTR is the difficulty in discriminating low grade tumor or peritumor regions that have an intact blood brain barrier (BBB) from normal brain tissues and delineating glioma margins during surgery. Here we present a highly sensitive, label-free terahertz reflectometry imaging (TRI) that overcomes current key limitations for intraoperative detection of World Health Organization (WHO) grade II (low grade), and grade III and IV (high grade) gliomas. We demonstrate that TRI provides tumor discrimination and delineation of tumor margins in brain tissues with high sensitivity on the basis of Hematoxylin and eosin (H&E) stained image. TRI may help neurosurgeons to remove gliomas completely by providing visualization of tumor margins in WHO grade II, III, and IV gliomas without contrast agents, and hence, improve patient outcomes.

B-cell CLL/lymphoma 3 promotes glioma cell proliferation and inhibits apoptosis through the oncogenic STAT3 pathway.

Aberrant expression of oncogenes and/or tumor suppressors play fundamental roles in the pathogenesis of glioma. B-cell CLL/lymphoma 3 (BCL3) was previously found to be a putative proto-oncogene in human cancers and the decoy receptor DcR1 is induced in a p50/Bcl3-dependent manner and attenuates the efficacy of temozolomide in glioblastoma cells. However, its expression status, clinical significance and biological functions in glioma remain largely unknown. In the present study, the levels of BCL3 were overexpressed in glioma compared to normal brain tissues. Furthermore, high expression of BCL3 protein was confirmed by immunoblotting in glioma cells as compared with normal human astrocyte cell line. The positive expression of BCL3 was correlated with adverse prognostic features and reduced overall survival rate of glioma patients. BCL3 silencing resulted in prominent decreased proliferation, cell cycle arrest in G1 phase and increased apoptosis in U251 cells. In contrast, BCL3 overexpression in U87 cells remarkably facilitated proliferative ability and cell cycle progression and induced apoptosis. Invivo studies showed that BCL3 knockdown inhibited the tumor growth of U251 cells in a mouse xenograft model. Mechanistically, BCL3 positively regulated the abundance of STAT3, p-STAT3 and the downstream targets of STAT3 pathway including BCL2, MCL-1 and cyclinD1 in glioma cells. Furthermore, a positive correlation between BCL3 and STAT3 expression was observed in glioma specimens. Notably, we confirmed that STAT3 knockdown abolished the oncogenic roles of BCL3 in glioma. In conclusion, we suggest that BCL3 serves as an oncogene in glioma by modulating proliferation, cell cycle progression and apoptosis, and its oncogenic effects are mediated by the STAT3 signaling pathway.