Comparison of two minimally invasive surgical approaches for hypertensive intracerebral hemorrhage: a study based on postoperative intracranial pressure parameters.

BACKGROUND: Increased intracranial pressure (ICP) in patients with hypertensive intracerebral hemorrhage (HICH) has been associated with poor prognosis. The transsylvian insular approach (TIA) and the transcortical (TCA) approach are applied for patients with HICH. We aimed to compare the postoperative ICP parameters of TIA and TCA to identify which procedure yields better short-term outcomes in patients with basal ganglia hematoma volumes ranging from 30 to 50 mL. METHODS: Eighty patients with basal ganglia hematomas 30-50 mL were enrolled in this study. Patients were implanted with ICP probes and divided into TIA and TCA groups according to the procedure. The ICP values were continuously recorded for five days at four-hour intervals. Short-term outcomes were evaluated using the length of hospitalization and postoperative consciousness recovery time. RESULTS: No statistically significant differences were found in age, sex, GCS score at admission, hematoma volume, and hematoma clearance rate (p > 0.05). The results showed that postoperative initial ICP, ICP on the first postoperative day, mean ICP, DICP20 mmHg × 4 h, postoperative consciousness recovery time, the length of hospitalization, mannitol utilization rate and the mannitol dosage were lower in the TIA group than in the TCA group (p < 0.05). Postoperative consciousness recovery time was positively correlated with ICP on the first postoperative day, and the length of hospitalization was positively correlated with mean ICP. CONCLUSIONS: TIA is more effective than TCA in improving the short-term outcomes of patients with basal ganglia hematoma volumes ranging from 30 to 50 mL according to comparisons of postoperative ICP parameters.

Development of prognostic indicator based on NAD+ metabolism related genes in glioma.

Background: Studies have shown that Nicotinamide adenine dinucleotide (NAD+) metabolism can promote the occurrence and development of glioma. However, the specific effects and mechanisms of NAD+ metabolism in glioma are unclear and there were no systematic researches about NAD+ metabolism related genes to predict the survival of patients with glioma. Methods: The research was performed based on expression data of glioma cases in the Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. Firstly, TCGA-glioma cases were classified into different subtypes based on 49 NAD+ metabolism-related genes (NMRGs) by consensus clustering. NAD+ metabolism-related differentially expressed genes (NMR-DEGs) were gotten by intersecting the 49 NMRGs and differentially expressed genes (DEGs) between normal and glioma samples. Then a risk model was built by Cox analysis and the least shrinkage and selection operator (LASSO) regression analysis. The validity of the model was verified by survival curves and receiver operating characteristic (ROC) curves. In addition, independent prognostic analysis of the risk model was performed by Cox analysis. Then, we also identified different immune cells, HLA family genes and immune checkpoints between high and low risk groups. Finally, the functions of model genes at single-cell level were also explored. Results: Consensus clustering classified glioma patients into two subtypes, and the overall survival (OS) of the two subtypes differed. A total of 11 NAD+ metabolism-related differentially expressed genes (NMR-DEGs) were screened by overlapping 5,995 differentially expressed genes (DEGs) and 49 NAD+ metabolism-related genes (NMRGs). Next, four model genes, PARP9, BST1, NMNAT2, and CD38, were obtained by Cox regression and least absolute shrinkage and selection operator (Lasso) regression analyses and to construct a risk model. The OS of high-risk group was lower. And the area under curves (AUCs) of Receiver operating characteristic (ROC) curves were >0.7 at 1, 3, and 5 years. Cox analysis showed that age, grade G3, grade G4, IDH status, ATRX status, BCR status, and risk Scores were reliable independent prognostic factors. In addition, three different immune cells, Mast cells activated, NK cells activated and B cells naive, 24 different HLA family genes, such as HLA-DPA1 and HLA-H, and 8 different immune checkpoints, such as ICOS, LAG3, and CD274, were found between the high and low risk groups. The model genes were significantly relevant with proliferation, cell differentiation, and apoptosis. Conclusion: The four genes, PARP9, BST1, NMNAT2, and CD38, might be important molecular biomarkers and therapeutic targets for glioma patients.

Development of a novel angiogenesis-related lncRNA signature to predict the prognosis and immunotherapy of glioblastoma multiforme.

Background: Long noncoding RNA (lncRNA) can regulate tumorigenesis, angiogenesis, proliferation, and other tumor biological behaviors, and is closely related to the growth and progression of glioma. The purpose of this research was to investigate the role of angiogenesis-related lncRNA in the prognosis and immunotherapy of glioblastoma multiforme (GBM). Methods: Differential analysis was carried out to acquire angiogenesis-related differentially expressed lncRNAs (AR-DElncRNAs). The AR-DElncRNAs were then subjected to univariate Cox and least absolute shrinkage and selection operator (LASSO) analyses to construct a prognostic model. Based on the median risk score, patients were classified into high-risk and low-risk groups. Kaplan-Meier survival analysis was conducted to estimate the prognostic value of the prognostic model. In addition, a nomogram was built to predict individual survival probabilities by combining clinicopathological characteristics and a prognostic model. Furthermore, immune infiltration, immunotherapy, and drug sensitivity analyses were administered to investigate the differences between the high- and low-risk groups. Results: We identified 3 lncRNAs (DGCR5, PRKAG2-AS1, and ACAP2-IT1) that were significantly associated with the survival of GBM patients from the 255 AR-DElncRNAs based on univariate Cox and LASSO analyses. Then, a prognostic model was structured according to these 3 lncRNAs, from which we found that high-risk GBM patients had a worse prognosis than that of low-risk patients. Moreover, the risk score was determined to be an independent prognostic factor [hazard ratio (HR) =1.444; 95% confidence interval (CI): 1.014-2.057; P<0.05]. The immune microenvironment analysis revealed that the immune score, stromal score, and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) score were significantly higher in the high-risk group than in the low-risk group. Neutrophils, macrophages, immature dendritic cells (iDCs), natural killer (NK) CD56dim cells, activated DCs (aDCs), and uncharacterized cells were different in the high- and low-risk groups. In addition, the high-risk group had a stronger sensitivity to immunotherapy. Furthermore, the sensitivity of 28 potential chemotherapeutic drugs differed significantly between the high- and low-risk groups. Conclusions: A novel angiogenesis-related lncRNA signature could be used to predict the prognosis and treatment of GBM.

Circ_RPPH1 regulates glioma cell malignancy by binding to miR-627-5p/miR-663a to induce SDC1 expression.

BACKGROUND: Recent studies revealed the key role of circular RNA (circRNA) in glioma progression. However, the effect of circ_0000520, also named as circRNA ribonuclease P RNA component H1 (circ_RPPH1), in glioma development was unknown. The study aimed to reveal the role of circ_RPPH1 in glioma cell malignancy. METHODS: Human astrocytes (NHA) and glioma cell lines (A172 and U251) were employed in this study. Quantitative real-time polymerase chain reaction and western blot were used to check the expression of circ_RPPH1, microRNA-627-5p (miR-627-5p), miR-663a and syndecan 1 (SDC1). Immunohistochemistry assay was conducted to assess the protein expression of nuclear proliferation marker ki67 and matrix metalloprotein 9 (MMP9). Cell viability was assessed by 3-(4,5-Dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell proliferation and apoptosis were investigated by flow cytometry analysis, 5-Ethynyl-29-deoxyuridine, or cell colony formation assay. Cell migration and invasion were evaluated by transwell assays. The interaction between miRNAs (miR-627-5p and miR-663a) and circ_RPPH1 or SDC1 was identified by a dual-luciferase reporter assay. A mouse model assay was performed to reveal the impact of circ_RPPH1 knockdown on glioma cell malignancy in vivo by analyzing neoplasm volume and weight. RESULTS: Circ_RPPH1 and SDC1 expression were significantly increased, whereas miR-627-5p and miR-663a expression were decreased in glioma tissues and cells in comparison with healthy brain tissues or human astrocytes. Circ_RPPH1 depletion led to the decreased cell proliferation, migration and invasion, and the increased cell apoptosis. Additionally, circ_RPPH1 bound to miR-627-5p/miR-663a and mediated glioma cell processes by interacting with them. SDC1 overexpression attenuated miR-627-5p/miR-663a-mediated actions. Moreover, circ_RPPH1 regulated SDC1 expression through interaction with miR-627-5p and/or miR-663a. Furthermore, circ_RPPH1 knockdown inhibited glioma cell malignancy in vivo, accompanied by the decreases of ki67 and MMP9 expression. CONCLUSION: Circ_RPPH1 knockdown inhibited glioma tumorigenesis by downregulating SDC1 by binding to miR-627-5p/miR-663a, showing that circ_RPPH1 might be an effective therapeutic target for glioma.

CircRNA circPTK2 Might Suppress Cancer Cell Invasion and Migration of Glioblastoma by Inhibiting miR-23a Maturation.

BACKGROUND: CircRNA circPTK2 plays opposite roles in different cancers, while its role in glioblastoma is unknown. The aim of this study was to explore the involvement of circPTK2 in glioblastoma. METHODS: Expression of circPTK2, mature miR-23a, and premature miR-23a in paired cancer and non-cancer tissues from glioblastoma patients (n = 60) was analyzed by RT-qPCR. Pearson's correlation coefficient was used to analyze the correlations between gene expressions. The effects of circPTK2 overexpression on miR-23a maturation were analyzed by transfecting circPTK2 expression vector into glioblastoma cells, followed by determining the expression of mature miR-23a and premature miR-23a by RT-qPCR. Transwell assays were carried out to explore the role of circPTK2 and miR-23a in regulating glioblastoma cell invasion and migration. RESULTS: We found that circPTK2 was downregulated in GBM and was inversely correlated with mature miR-23a, but not premature miR-23a. GBM cells transfected with circPTK2 expression vector showed significantly downregulated mature miR-23a, but not premature miR-23a. Transwell assay analysis showed that circPTK2 overexpression decreased cell invasion and migration, while miR-23a increased cell invasion and migration. Moreover, miR-23a overexpression reversed the inhibitory effects of circPTK2 overexpression on cell behaviors. CONCLUSION: CircPTK2 might suppress cancer cell invasion and migration by inhibiting the maturation of miR-23a.

Identification of an epigenetic prognostic signature for patients with lower-grade gliomas.

INTRODUCTION: Glioma is the most common malignant primary brain tumor with survival outcome for patients with lower-grade gliomas (LGGs) being quite variable. Epigenetic modifications in LGGs appear tightly linked to patient clinical outcomes but are not commonly used as clinical tools. AIMS: We aimed to derive an epigenetic enzyme gene signature for LGGs that would allow for improved clinical risk stratification. RESULTS: The study employed transcriptomic data of 711 lower-grade gliomas from three publically available data sets. Based on least absolute shrinkage and selection operator (LASSO) Cox regression analysis, we discovered a 13-gene epigenetic signature that strongly predicts poor overall survival in LGGs. The robust prediction ability for survival was further verified in two independent validation cohorts. The signature was also significantly associated with malignant molecular signatures including wild-type IDH, unmethylated MGMT promoter, and non-codeletion of 1p19q together with linkage to multiple oncogenic pathways. Interestingly, our results showed that immune infiltration of MDSCs together with mRNA expression of immune inhibition biomarkers was also positively correlated with the epigenetic signature. Lastly, we confirmed the oncogenic role of SMYD2 in glioma tumor cells in functional assays. CONCLUSIONS: We report a novel epigenetic gene signature that harbors robust survival prediction value for LGG patients that is tightly linked to activation of multiple oncogenic pathways.

Long intergenic noncoding RNA 00021 promotes glioblastoma temozolomide resistance by epigenetically silencing p21 through Notch pathway.

Increasing findings are suggesting the vital roles of long noncoding RNAs (lncRNAs) in the glioblastoma tumorigenesis. However, whether the novel lncRNA LINC00021 modulates temozolomide (TMZ) resistance of glioblastoma is still unclear. Clinically, lncRNA LINC00021 was significantly up-regulated in glioblastoma, especially the TMZ-resistant tissue and cells, and the LINC00021 overexpression was closely correlated to TMZ resistance and unfavorable prognosis. Functionally, LINC00021 positively promoted the TMZ resistance and reduced apoptosis. Mechanistically, transcription factor E2F1 activated the expression of LINC00021. Moreover, LINC00021 regulated the glioblastoma TMZ resistance through Notch pathway and epigenetically silenced p21 expression via recruiting EZH2. Collectively, present research indicates the critical roles of lncRNA LINC00021 in glioblastoma genesis, providing a novel insight for TMZ resistance in glioblastoma.

Efficacy of percutaneous vertebroplasty treatment of spinal tumors: A meta-analysis.

OBJECTIVE: To evaluate the function of percutaneous vertebroplasty (PVP) treatment to pain relief and life quality for patients with spinal tumors. METHODS: Articles about the researches on the treatment of spinal tumors by PVP in PubMed, Embase, and the Chinese Biomedical Literature database from January 1, 2015 to December 31, 2013. The keywords "spinal tumors," "efficacy," and "vertebroplasty" were firstly scanned to exclude all irrelevant articles. Then, the final inclusion of studies was determined by reading the full text of the remaining articles. The citation lists of all retrieved articles were scanned to identify other potentially relevant reports. RevMan5.2 was used to analyze pain intensity visual analog scale (VAS) and Karnofsky performance scores (KPS) within each research. Combined HRs (hazard ratio) were calculated using fixed- or random- effects models according to the heterogeneity. RESULTS: Twenty-six studies involving 1351 patients met our selection criteria. Meta-analysis results among 10 case-control studies showed that the combined HR was -2.83 [95% confidence interval (CI) -2.92, -2.73; P < .0001], indicating a 2.83-fold decrease of pain in PVP group. For 12 single-arm studies, a significantly decrease of pain after PVP treatment (HR = -4.79, 95% CI -5.00, -4.57, P < .0001) was also found in PVP group. In addition, for KPS analysis, the combined HR was 16.31 (95% CI 14.31, 18.31; P < .0001), which indicated that PVP treatment was associated with a 16.31-fold increase of KPS. The combined HR was 0.58 (95% CI 0.35, 0.96; P = .04) for complication analysis. CONCLUSIONS: PVP treatment of spinal tumor is significantly associated with better pain relief and life quality, which could improve the outcome in metastatic spinal tumor patients.

Targeting dual specificity protein kinase TTK attenuates tumorigenesis of glioblastoma.

Accumulating evidence has proved that glioma stem-like cells (GSCs) are responsible for tumorigenesis, treatment resistance, and subsequent tumor recurrence in glioblastoma (GBM). In this study, we identified dual specificity protein kinase TTK (TTK) as the most up-regulated and differentially expressed kinase encoding genes in GSCs. Functionally, TTK was essential for in vitro clonogenicity and in vivo tumor propagation in GSCs. Clinically, TTK expression was highly enriched in GBM, moreover, was inversely correlated with a poor prognosis in GBM patients. Mechanistically, mitochondrial fission regulator 2 (MTFR2) was identified as one of the most correlated genes to TTK and transcriptionally regulated TTK expression via activation of TTK promoter. Collectively, MTFR2-dependent regulation of TTK plays a key role in maintaining GSCs in GBM and is a potential novel druggable target for GBM.

Angiotensin-converting enzyme insertion/deletion gene polymorphisms is associated with risk of glioma in a Chinese population.

INTRODUCTION: The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene has recently been linked to the pathogenesis and progression of human cancers. The aim of this study was to evaluate the potential association between ACE I/D polymorphism and glioma in a Chinese population. MATERIALS AND METHODS: A case-control study involving patients with 800 glioma and 800 controls was conducted. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay was applied to assess the ACE I/D genotypes. RESULTS: Glioma cases had a significantly higher frequency of DD genotype [odds ratio (OR) = 1.61, 95% confidence interval (CI) = 1.12, 2.32; p = 0.01] than controls. When stratified by the grade of glioma, cases with WHO IV glioma had a significantly higher frequency of DD genotype (OR = 1.51, 95% CI = 1.03, 2.21; p = 0.03). When stratified by the histology of glioma, there was no significant difference in the distribution of each genotype. CONCLUSION: Our study suggested that the ACE DD genotype was associated with a higher glioma risk in this Chinese population. To the best of our knowledge, this is the first report describing the potential association between ACE I/D polymorphism and glioma. Additional studies are needed to confirm this finding.

Increased 8-hydroxydeoxyguanosine in high-grade gliomas is associated with activation of autophagy.

AIM OF THE STUDY: To understand the interaction between oxidative stress and autophagy in gliomas of different grades. MATERIALS AND METHODS: In the present study, we analyzed levels of oxidative stress in 45 human glioma tumors, using the DNA oxidation marker 8-hydroxydeoxyguanosine (8-OHdG). In addition, we determined activation of autophagy in gliomas samples by assessing expression of microtubule-associated protein 1 light chain-3B (LC3B). To confirm our in vivo findings, in vitro studies using U87 cells were conducted. RESULTS: It was determined that the grade of gliomas, that is, different malignant degrees according to WHO classification, significantly affected level of 8-OHdG. High levels of 8-OHdG were present in high-grade gliomas. This trend was significant in male patients and in young adult patients (<50 years old). Further study showed increased expression of LC3B in high-grade gliomas. In addition, levels of 8-OHdG and expression of LC3B were positively correlated. Reducing autophagic activity by 3-methyladenine resulted in significantly increased intracellular reactive oxygen species (ROS) in U87 cells. CONCLUSIONS: Our study provides evidence that high levels of oxidative stress in high-grade gliomas are associated with autophagy activation that may play a protective role promoting the survival of high-grade gliomas under severe oxidative stress.

Three single nucleotide polymorphisms of the vascular endothelial growth factor (VEGF) gene and glioma risk in a Chinese population.

OBJECTIVE: To investigate the association between three single nucleotide polymorphisms (SNPs) of the vascular endothelial growth factor (VEGF) gene and the risk of glioma in a Han Chinese population. METHODS: This hospital-based case-control study used polymerase chain reaction-restriction fragment length polymorphism analysis to detect three SNPs (-634 G/C, +936 C/T and +1612 G/A) of the VEGF gene in patients with glioma compared with healthy control subjects. RESULTS: The study investigated 880 patients with gliomas and 880 age- and sex-matched healthy control subjects. Patients with gliomas had a significantly higher frequency of the -634 CC genotype (odds ratio [OR] 1.35, 95% confidence interval [CI] 1.05, 1.75) and the +936 TT (OR 1.73, 95% CI 1.20, 2.48) genotype compared with the control subjects. Patients with glioblastomas had a significantly higher frequency of the -634 CC and +936 TT genotypes. Patients with grade IV gliomas had a significantly higher frequency of the -634 CC and +936 TT genotypes. The +1612 G/A polymorphisms were not associated with glioma risk. CONCLUSION: The VEGF - 634 CC and +936 TT genotypes were associated with a higher risk of glioma in a Han Chinese population.