Risk factors of acute ischemic stroke and the role of angiotensin I in predicting prognosis of patients undergoing endovascular thrombectomy.

Purpose: The interaction between the renin-angiotensin system (RAS) and the acute ischemic stroke (AIS) is definite but not fully understood. This study aimed to analyze the risk factors of AIS and explore the role of serum indicators such as angiotensin I (Ang I) in the prognosis of patients undergoing endovascular thrombectomy (EVT). Patients and methods: Patients with AIS who underwent EVT and healthy controls were retrospectively enrolled in this study, and the patients were divided into a good or a poor prognosis group. We compared Ang I, blood routine indexes, biochemical indexes, electrolyte indexes, and coagulation indexes between patients and controls. We used univariate and multivariate logistic regression analyses to evaluate possible risk factors for AIS and the prognosis of patients undergoing EVT. Independent risk factors for the prognosis of patients undergoing EVT were identified through multifactorial logistic regression analyses to construct diagnostic nomograms, further assessed by receiver operating characteristic curves (ROC). Results: Consistent with previous studies, advanced age, high blood glucose, high D-dimer, and high prothrombin activity are risk factors for AIS. In addition, Ang I levels are lower in AIS compared to the controls. The level of Ang I was higher in the good prognosis group. Furthermore, we developed a nomogram to evaluate its ability to predict the prognosis of AIS after EVT. The AUC value of the combined ROC model (Ang I and albumin-globulin ratio (AGR)) was 0.859. Conclusions: In conclusion, advanced age, high blood glucose, high D-dimer, and high prothrombin activity are risk factors for AIS. The combined Ang I and AGR model has a good predictive ability for the prognosis of AIS patients undergoing arterial thrombectomy.

The value of modified hijdra score in patients with aneurysmal subarachnoid hemorrhage.

Background: The complexity of calculating the Hijdra score has limited its clinical utility in aiding the diagnosis of intracranial ruptured aneurysms. Objective: This study aimed to investigate the diagnostic and prognostic value of the modified Hijdra score in patients with aneurysmal subarachnoid hemorrhage (aSAH). Methods: Data from 773 patients with subarachnoid hemorrhage (SAH) at the First People's Hospital of Lianyungang from January 2018 to June 2023 were collected. The modified Hijdra scoring method simplifies the assessment of 10 basal cisterns/cisterns fissures compared to the traditional scoring method, with scores ranging from 0 to 2 for each item, and assigns specific scores to hematomas larger than 1 cm in diameter. The data were divided into an evaluation group (n = 641) and a validation group (n = 132). In the evaluation group, the performance of the modified Hijdra score in diagnosis and prognostic prediction was assessed, while the diagnostic and prognostic prediction efficacy of the modified Hijdra method was evaluated using the validation set. Results: Among the 641 patients in the evaluation group,550 (85. 8%) were diagnosed with intracranial aneurysms. The modified Hijdra score demonstrated an AUC of 0. 894 for aneurysm diagnosis, with a sensitivity of 98. 0% and a specificity of 64. 8% at a CutOff value of 7. 5. The diagnostic efficacy of the modified Hijdra score was 93. 24%, with a negative predictive value of 84. 29%, while the Hijdra score 's diagnostic efficacy was 85. 34% with a negative predictive value of 48. 89%. The AUC of the modified Hijdra score for predicting prognosis in patients with aneurysms was 0. 824, with a sensitivity of 84. 3% and a specificity of 70. 0% at a CutOff value of 16. 5. In CTA-negative patients, the modified Hijdra score was significantly higher (P < 0. 0001) in patients with aneurysmal SAH (15. 48 ± 3. 93) compared to those with non-aneurysmal SAH (6. 31 ± 4. 52). Conclusions: The modified Hijdra score is a valuable tool for assisting in the diagnosis and prognosis prediction of aneurysmal subarachnoid hemorrhage.

The new morphologic classification of the hand motor cortex with magnetic resonance imaging in glioma patients.

Purpose: The hand motor cortex (HMC) is a reliable anatomical landmark for identifying the precentral gyrus. The current study aimed to investigate the morphology of HMC on axial MRI of glioma patients, propose a new morphological classification of HMC and analyze the effect of tumors on the morphology of HMC. Methods: A retrospective study of 276 adult right-handed glioma patients was conducted. The morphology of HMC was assessed using T2 axial images. Subsequently, the distribution of morphological subtypes was compared between the bilateral hemispheres and the tumor-affected and healthy hemispheres. Finally, the influence of tumor pathology on the morphology of HMC was investigated. Results: A new morphological classification of HMC with four subtypes (Ω, ε, Ω-ε and ε-Ω) was proposed. No significant difference was identified in the distribution of morphological subtypes between the bilateral hemispheres (p = 0.0901, Chi-square test), or between the tumor-affected and healthy hemispheres (p = 0.3507, Chi-square test), and the morphology of HMC between the bilateral hemispheres were consistent (p < 0.0001, Kappa test). In addition, a significant difference was identified in the distribution of morphological subtypes between astrocytic and oligodendroglial tumors (p = 0.0135, Chi-square test). Conclusion: In the current study, we proposed a new morphological classification of HMC, and found that tumor could affect the morphology of HMC in glioma patients. The results can help our clinical practice, enabling us to further understand the spatial structure of the cerebral hemispheres.

LncRNA NEAT1 facilitates glioma progression via stabilizing PGK1.

BACKGROUND: Long noncoding RNA NEAT1 has been implicated in glioma progression. However, the effect of NEAT1 on glycolysis of glioma cell and the potential mechanism remain unclear. METHODS: In vitro experiments, including CCK-8, colony formation, ECAR, and lactate detection assays were performed to evaluate the effect of NEAT1 on proliferation and glycolysis of glioma cell. RNA pulldown and RIP assays were performed to identify the interaction between NEAT1 and PGK1. Truncated mutation of NEAT1 and PGK1 was used to confirm the specific interactive domains between NEAT1 and PGK1. Animal studies were performed to analyze the effect of NEAT1/PGK1 on glioma progression. RESULTS: NEAT1 knockdown significantly suppressed the proliferation and glycolysis of glioma cells. NEAT1 could specifically interact with PGK1, which promotes PGK1 stability. Hairpin A of NEAT1 is essential for interaction with M1 domain of PGK1. Depletion of NEAT1 markedly inhibited tumor growth in mice, while PGK1 could reverse this effect. Higher expression of NEAT1 was associated with poor overall survival of GBM patients. CONCLUSIONS: NEAT1 over expression promotes glioma progression through stabilizing PGK1. NEAT1/PGK1 axis is a candidate therapeutic target for glioma treatment.

Bilateral carotid cavernous fistula after trauma: a case report and literature review.

BACKGROUND: Carotid cavernous fistula is a rare complication that is typically associated with head trauma and skull base fractures. The traumatic bilateral carotid cavernous fistula are significantly rarer. CASE PRESENTATIONS: We report a case of a 61-year-old man presenting with unilateral exophthalmos, swollen eyelids, conjunctival congestion, and edema etiologically associated with severe trauma. Thereafter, the patient demonstrated symptoms of contralateral oculomotor nerve injury caused by skull base fracture, such as ptosis of eyelid, dilated pupils, and eye movement disorder, and was diagnosed with bilateral carotid cavernous fistula. CONCLUSIONS: The patient recovered after undergoing endovascular embolization of bilateral cavernous sinus fistulas. The patient demonstrated the classic symptoms of an extremely rare condition known as bilateral carotid cavernous fistula, in only one eye. Reporting and analyzing this case will help us elucidate the underlying mechanisms of this disease.

HLA-E expression in diffuse glioma: relationship with clinicopathological features and patient survival.

BACKGROUND: Human leukocyte antigen-E (HLA-E) has been extensively investigated in various human cancers including glioma. However, the clinical significance of HLA-E expression in glioma patients has not been elucidated. The current study aimed to investigate the association of HLA-E expression with clinicopathological features and survival in patients with diffuse glioma. METHODS: A total of 261 glioma patients were enrolled, subsequently, mRNA microarray analysis was conducted to identify the relationship of HLA-E with clinicopathological features and patient survival. RESULTS: HLA-E was significantly overexpressed in high-grade gliomas compared to low-grade gliomas (LGGs). Moreover, HLA-E expression was significantly higher in diffuse astrocytomas than oligodendrogliomas (p = 0.032, t-test). Kaplan-Meier analysis showed that progression-free survival (PFS) and overall survival (OS) were significantly better in LGG patients with low HLA-E expression (p = 0.018 for PFS and p = 0.020 for OS, Log-rank test). Furthermore, HLA-E expression was identified to be an independent prognostic factor by Cox analysis (p = 0.020 for PFS and p = 0.024 for OS). CONCLUSIONS: This is the first study which identified the clinical significance of HLA-E in diffuse glioma. HLA-E expression was correlated with more aggressive tumor grade and histological type and was identified as an independent prognostic biomarker in LGG patients.

Genetic and clinical characterization of B7-H3 (CD276) expression and epigenetic regulation in diffuse brain glioma.

Gliomas are the most common malignant tumors of the brain. Immune checkpoints have been increasingly emphasized as targets for treating malignant tumors. B7-H3 has been identified as an immune checkpoint that shows potential value for targeting therapies. We set out to characterize the expression pattern and biological function of B7-H3 in brain gliomas using high-throughput data obtained from the Chinese Glioma Genome Atlas (CGGA) and the Cancer Genome Atlas (TCGA) projects. B7-H3 was upregulated more in higher-grade gliomas than that in lower-grade gliomas in both CGGA and TCGA datasets. Isocitrate dehydrogenase (IDH) mutation seemed to exert significant influence on B7-H3 expression in gliomas but led to quite different results between grade II gliomas and higher-grade gliomas. In addition to IDH, methylation of B7-H3 promoter and microRNA-29 family also showed a potential regulatory effect on B7-H3 expression. Gene ontology analysis revealed that B7-H3 was associated with mitotic cell cycle, cell proliferation and immune response. Further investigation suggested that B7-H3 was mostly involved in the Toll-like receptor signaling pathway. Survival analysis indicated that B7-H3 was an independent unfavorable prognosticator for glioma patients in both CGGA and TCGA datasets. B7-H3 expression is regulated by multiple mechanisms and is potentially involved in the T-cell receptor signaling pathway. Higher B7-H3 expression indicates a worse prognosis for glioma patients, which warrants further research into the development of inhibitors for targeting this immune checkpoint, but we still need to be cautious about immune checkpoint inhibition for central nervous system tumors.

MEGF10, a Glioma Survival-Associated Molecular Signature, Predicts IDH Mutation Status.

Glioma is the most common primary brain tumor with various genetic alterations; among which, IDH mutation is the most common mutation and plays an important role in glioma early development, especially in lower grade glioma (LGG, WHO II-III). Previous studies have found that IDH mutation is tightly associated with extensive methylation across whole genome in glioma. To further investigate the role of IDH, we obtained methylation data of 777 samples from CGGA (Chinese Glioma Genome Atlas) and TCGA (The Cancer Genome Atlas) with IDH mutation status available. A package compiled under R language called Tspair was used as the main analytic tool to find potential probes that were significantly affected by IDH mutation. As a result, we found one pair of probes, cg06940792 and cg26025891, which was capable of predicting IDH mutation status precisely. The hypermethylated probe was cg06940792, designed in the promoter region of MEGF10, while the hypomethylated probe was cg26025891, designed in the promoter region of PSTPIP1. Survival analysis proved that hypermethylation or low expression of MEGF10 indicated a favorable prognosis in 983 glioma samples. Moreover, gene ontology analysis demonstrated that MEGF10 was associated with cell migration, cell proliferation, and regulation of apoptosis in glioma. All findings above can be validated in three other independent cohorts. In a word, our results suggested that methylation level and mRNA expression of MEGF10 in glioma were not only correlated with IDH mutation but also associated with clinical outcome of patients, providing potential guide for future dissection of IDH role in glioma.

Identification of a DNA Repair-Related Multigene Signature as a Novel Prognostic Predictor of Glioblastoma.

BACKGROUND: Glioblastoma (GBM) is an extremely challenging malignancy to treat. Although temozolomide (TMZ) is a standard treatment regimen, many patients with GBM develop chemoresistance. The aim of this study was to identify a DNA repair-related gene signature to better stratify patients treated with TMZ. METHODS: We selected 89 cases of primary GBM (pGBM) from the Chinese Glioma Genome Atlas RNA-seq dataset as the training cohort, whereas The Cancer Genome Atlas RNA-seq and Gene Set Enrichment (GSE) 16011 mRNA array sets were used as validation cohorts. Regression analysis and linear risk score assessment were performed to build a DNA repair-related signature. We used Kaplan-Meier analysis to evaluate the predictive value of the signature for overall survival (OS) in the different groups. Multivariate Cox regression analysis was used to determine whether the 5-gene signature could independently predict OS. RESULTS: Using our 5-gene signature panel of APEX1, APRT, PARP2, PMS2L2, and POLR2L, we divided patients with pGBM into high- and low-risk groups. Patients with a low-risk score were predicted to have favorable survival and greater benefit from TMZ therapy compared with patients from the high-risk group (P < 0.05). Moreover, receiver operating characteristic curves showed that the multigene signature was the most sensitive and specific model for survival prediction (P < 0.05). CONCLUSIONS: Among patients with pGBM, classification based on a risk score determined using a 5-gene panel indicated different OS and reaction to TMZ. The findings in this study demonstrate that this unique 5-gene signature could be a novel model to predict OS and provide accurate therapy for patients with pGBM.

Overexpression of Paxillin Correlates with Tumor Progression and Predicts Poor Survival in Glioblastoma.

AIMS: To explore the prognostic and clinicopathological features of glioma with Paxillin (PXN) expression based on a large number of samples. METHODS: RNA sequencing data of 325 glioma samples from Chinese Glioma Genome Atlas (CGGA) database were obtained as discovery set. Three additional datasets were further obtained as validation sets. The protein expression pattern of PXN in glioma was measured by IHC. Kaplan-Meier survival and multivariate Cox analysis were used to estimate the survival distributions. Moreover, the functional annotation of PXN was also analyzed. RESULTS: In the discovery set, PXN overexpression was significantly associated with high-grade glioma as well as the higher mortality in survival analysis (log-rank test, P < 0.01). The results of the other validation datasets showed similar findings. PXN also served as an independent prognostic biomarker in glioblastoma patients. Functional assays showed that PXN contributed to glioma cell proliferation and invasion. CONCLUSION: PXN plays as an oncogene in glioma progression and suggests a new potential biotarget for therapy.

The Landscape of Viral Expression Reveals Clinically Relevant Viruses with Potential Capability of Promoting Malignancy in Lower-Grade Glioma.

Purpose: RNA sequencing (RNA-seq) has recently proved to be effective for revealing novel virus-tumor associations. To get a thorough investigation of virus-glioma associations, we screened viruses in gliomas with RNA-seq data from the Chinese Glioma Genome Atlas project.Experimental Design: In total, 325 samples were enrolled into this study. Reads that failed to map to the human genome were aligned to viral genomes and screened for potential virus-derived transcripts. For quantification, VPKM was calculated according to mapped reads weighted by genome sizes and sequencing depth.Results: We observed that viruses tended to concertedly express in a certain subgroup of patients. Survival analysis revealed that individuals who were infected with Simian virus 40 (SV40) or woolly monkey sarcoma virus (WMSV) had a significantly shorter overall survival than those uninfected. A multivariate Cox proportional hazards model, taking clinical and molecular factors into account, was applied to assess the prognostic value of SV40 and WMSV. Both SV40 and WMSV were independent prognostic factors for predicting patient's survival in lower-grade gliomas. Subsequent gene analysis demonstrated that SV40 was correlated with regulation of transcription, whereas WMSV was correlated with cell-cycle phase, which indicated frequent proliferation of tumor cells.Conclusions: RNA-seq was sufficient to identify virus infection in glioma samples. SV40 and WMSV were identified to be prognostic markers for patients with lower-grade gliomas and showed potential values for targeting therapy. Clin Cancer Res; 23(9); 2177-85. ©2016 AACR.

Molecular and clinical characterization of PD-L1 expression at transcriptional level via 976 samples of brain glioma.

Background: PD-L1 has been widely reported as immune check points in a range of malignancies as well as some immune-originated diseases. In glioma, the role of PD-L1 remains unclear. We aimed at investigating its role at transcriptome level and relationship with clinical practice. Method and patients: In total, 976 glioma samples with transcriptome data, including 301 microarray data from Chinese Glioma Genome Atlas (CGGA project) and 675 RNAseq data from TCGA project, were enrolled into our study. Clinical and IDH mutation data were also available. R language was used as the main tool for statistical analysis and graphical work. Results: PD-L1 expression was found to be positively correlated with WHO grade of glioma. PD-L1 seemed to express more in mesenchymal subtype according to TCGA transcriptional classification scheme and may contribute as a potential marker for mesenchymal subtype in glioblastoma. Pearson correlation test indicated that PD-L1 showed robust correlation with PD1, PD-L2, and CD80 in CGGA dataset. Subsequent gene ontology analysis based on significantly correlated genes of PD-L1 revealed that PD-L1 seemed to be profoundly associated with T cell activation. To further investigate the relationship between PD-L1 expression and immune response, we selected a series of immune signatures, which were then transformed into metagenes, and found that PD-L1 expression was particularly paralleled with T-cells and macrophages-related immune response instead of B cell linage-related immune response. In line with the corresponding biological process, PD-L1 exhibited predictive value for glioma patients: Higher PD-L1 indicated significantly shorter survival, especially in glioblastoma. Conclusion: PD-L1 is upregulated in glioblastoma, and is synergistic with other check point members. Moreover, PD-L1 is significantly associated with T-cell activation and macrophage-related immune response and predicts much worse survival for patients, warranting clinical trials of PD1/PD-L1 checkpoint inhibitors for potential glioma treatment.

FGFR3, as a receptor tyrosine kinase, is associated with differentiated biological functions and improved survival of glioma patients.

BACKGROUND: Activation of receptor tyrosine kinases is common in Malignancies. FGFR3 fusion with TACC3 has been reported to have transforming effects in primary glioblastoma and display oncogenic activity in vitro and in vivo. We set out to investigate the role of FGFR3 in glioma through transcriptomic analysis. RESULTS: FGFR3 increased in Classical subtype and Neural subtype consistently in CGGA and TCGA cohort. Similar patterns of FGFR3 distribution through subtypes were observed in CGGA and TCGA samples. Gene ontology analysis was performed with genes that were significantly correlated with FGFR3 expression. We found that positively associated biological processes of FGFR3 were focused on differentiated cellular functions and neuronal activities, while negatively correlated biological processes focused on mitosis and cell cycle phase. Clinical investigation showed that higher FGFR3 expression predicted improved survival for glioma patients, especially in Proneural subtype. Moreover, FGFR3 showed very limited relevance with other receptor tyrosine kinases in glioma at transcriptome level. MATERIALS AND METHODS: FGFR3 expression data of glioma was obtained from Chinese Glioma Genome Atlas (CGGA) and TCGA (The Cancer Genome Atlas). In total, RNA sequencing data of 325 glioma samples and mRNA microarray data of 301 samples from CGGA dataset were enrolled into this study. To consolidate the findings that we have revealed in CGGA dataset, RNA-seq data of 672 glioma samples from TCGA dataset were used as a validation cohort. R language was used as the main tool to perform statistical analysis and graphical work. CONCLUSIONS: FGFR3 expression increased in classical and neural subtypes and was associated with differentiated cellular functions. FGFR3 showed very limited correlation with other common receptor tyrosine kinases, and predicted improved survival for glioma patients.