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Accumulating evidence has revealed that survivin expression is associated with a malignant phenotype and poor prognosis in glioma. Survivin is also a potential target of microRNA (miRNA/miR)-218. The aim of the present study was to investigate the expression and function of survivin in glioblastoma, and to examine the association between survivin and miR-218. For that purpose, survivin mRNA levels were analyzed in 144 frozen samples of glioblastoma using whole-genome RNA sequencing. In vitro cell proliferation, migration, invasion and apoptosis assays were performed, and survivin expression was detected by western blotting. The results revealed that the mRNA expression levels of survivin were negatively and significantly associated with overall survival in glioblastoma. Further in vitro analyses suggested that miR-218 may inhibit the expression of survivin. Expression of miR-218 in the LN229 cell line was significantly lower than that in the immortalized human gliocyte HEB cell line. miR-218 markedly inhibited tumor cell proliferation, migration and invasion capacities, and decreased apoptosis. miR-218 also inhibited the expression of survivin. These results indicated that survivin may be a target of miR-218 and could serve as a predictive biomarker. [ABSTRACT FROM AUTHOR]

Different gene expression and methylation profiles are identified in glioblastoma (GBM). To screen the differentially expressed genes affected by DNA methylation modification and further investigate their prognostic values for GBMs. We included The Cancer Genome Atlas (TCGA) RNA sequencing (676) and DNA methylation (Illumina Human Methylation 450K; 657) databases to detect the gene expression and methylation profiles. Chinese Glioma Genome Atlas (CGGA) RNA sequencing database and TCGA DNA methylation (Illumina Human Methylation 27K; 283) was included for validation. Gene expression and DNA methylation statues were identified using principal components analysis (PCA). A total of 3365 differentially expressed genes were identified. Among them, 2940 genes showed low methylation and high expression, while 425 genes showed high methylation and low expression in GBMs. An eight-gene (C9orf64, OSMR, MDK, MARVELD1, PTRF, MYD88, BIRC3, RPP25) signature was established to divide GBM patients into two groups based on the cut-off point (27.24). The high risk group had shorter overall survival (OS) than low risk group (median OS 15.77 vs. 10.61 months; P = 0.0002). Moreover, the different clinical and molecular features were shown between two groups. These findings could be validated in additional datasets. The differentially expressed genes affected by DNA methylation modification were detected. Our results showed that the eight-gene signature has independently prognostic value for GBM patients. [ABSTRACT FROM AUTHOR]

Introduction: Contrast enhancement observable on magnetic resonance (MR) images reflects the destructive features of malignant gliomas. This study aimed to investigate the relationship between radiologic patterns of tumor enhancement, extent of resection, and prognosis in patients with anaplastic gliomas (AGs). Methods: Clinical data from 268 patients with histologically confirmed AGs were retrospectively analyzed. Contrast enhancement patterns were classified based on preoperative T1-contrast MR images. Univariate and multivariate analyses were performed to evaluate the prognostic value of MR enhancement patterns on progression-free survival (PFS) and overall survival (OS). Results: The pattern of tumor contrast enhancement was associated with the extent of surgical resection in AGs. A gross total resection was more likely to be achieved for AGs with focal enhancement than those with diffuse ( p = 0.001) or ring-like ( p = 0.024) enhancement. Additionally, patients with focal-enhanced AGs had a significantly longer PFS and OS than those with diffuse (log-rank, p = 0.025 and p = 0.031, respectively) or ring-like (log-rank, p = 0.008 and p = 0.011, respectively) enhanced AGs. Furthermore, multivariate analysis identified the pattern of tumor enhancement as a significant predictor of PFS ( p = 0.016, hazard ratio [HR] = 1.485) and OS ( p = 0.030, HR = 1.446). Conclusion: Our results suggested that the contrast enhancement pattern on preoperative MR images was associated with the extent of resection and predictive of survival outcomes in AG patients. [ABSTRACT FROM AUTHOR]

Background As the population ages, the proportion of elderly patients with glioblastomas has increased. Recently, many researchers have focused on the treatments available to and prognoses in elderly patients with glioblastomas. Methods We conducted a retrospective study of glioblastoma patients aged 60 years old or older who were treated at the Neurosurgery Center at Beijing Tiantan Hospital from 2012 to 2014. Their clinical features, immunohistochemical characteristics, treatments, and outcomes were evaluated to determine treatment tolerance and identify prognostic factors. Results Among the 70 included patients, the median survival time was 15 months. In the univariate analysis, patients who underwent a gross total resection had longer overall survival times than patients who had a subtotal resection ( P < 0.05), and patients who received postoperative adjuvant therapy had longer overall survival times than those with no postoperative adjuvant therapy ( P < 0.05). The expression of the p53 protein significantly affected overall survival. Patients with low p53 protein expression had a median survival of 17 months, whereas those who had high p53 protein expression had a median survival of 11.50 months ( P < 0.05). Undergoing a gross total resection, receiving postoperative adjuvant therapy and having low p53 protein expression were factors that independently contributed to longer overall survival times in multivariate analysis. Conclusions Maximal safe surgical resection followed by radiotherapy with concurrent and adjuvant temozolomide significantly prolonged overall survival times and was well tolerated in elderly patients with glioblastomas. In addition, low p53 protein expression was a significant favorable prognostic indicator in this population. [ABSTRACT FROM AUTHOR]

Age is a powerful prognostic factor of high-grade glioma (HGG). However, the underlying genetic mechanisms of the discrepant prognosis among different age groups remain elusive. A total of 953 and 559 HGG patients from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) cohorts were enrolled and assigned as young, intermediate, elderly groups. The data of clinicopathological characteristics, mRNA, mutation, copy number alteration was analyzed. Transcriptomic analysis revealed that diverse biological processes including immune response are altered between the young and elderly groups. Combined with the analysis of infiltrating immune cells and immune checkpoints, our results suggest an immune suppression status in the elderly group. Patients from different age groups exhibit different mutation and copy number alteration profiles. A multi-omics analysis is conducted to explore the biological basis of HGG patients of different age groups. This study suggests an immune-suppressive environment in elderly patients. [Display omitted] • Immune suppression is remarkable in the elderly patients of HGG. • Mutation landscape varies among the age groups. • Diverse biological processes are altered with age of HGG patients. [ABSTRACT FROM AUTHOR]

Tumor-associated macrophages (TAMs) are regarded as the most abundantly infiltrating immune cells around the tumor microenvironment in gliomas, which plays an important role in tumorgenesis and immunosuppression. A total of 216 patients diagnosed with primary glioma were obtained from the Chinese Glioma Genome Atlas of which the RNA sequencing data was used as training set. RNA sequencing from the Cancer Genome Atlas was applicated for validation. We found that mesenchymal subtype showed strong positive correlation with macrophage-related genes (MRGs) expression. Survival analysis showed that high expression level of MRG predicted poor prognosis. A TAM-based nine-gene signature was constructed, which divided the samples into high- and low-risk of unfavorable outcome. The result of Cox regression analysis showed that the risk score was an independent prognostic factor in gliomas. Hence, the expression of TAMs was correlated with patient survival. The nine-TAM-related gene signature can predict patient survival efficiently. • Tumor-associated macrophages (TAMs) possesses the most part of the tumor microenvironment in gliomas. • High expression level of macrophage-related genes indicates a poor prognosis. • A TAM-based nine-gene signature can predict patient survival in gliomas. [ABSTRACT FROM AUTHOR]