Factor In Glioma Research Articles

IMMU-29. AIF1 IS A PROGNOSTIC BIOMARKER AND CORRELATED WITH IMMUNE INFILTRATES IN GLIOMAS

Gliomas remain highly variable clinical behaviors, leading to emerging studies to identify prognostic factors. AIF1 (Allograft Inflammatory Factor 1) is critical for promoting both macrophage- and dendritic cells (DCs)-mediated inflammatory response and growth of vascular smooth muscle cells and T-lymphocytes. Through comparative analyses of primary LGG patients from The Cancer Genome Atlas (TCGA) dataset and Chinese Glioma Genome Atlas(CGGA) dataset, we reported that the expression level and methylation level of AIF1 gene vary among glioma patients and AIF1 expression or gene body methylation is significantly associated with glioma patient survival. Cox regression results confirmed that AIF1 played an independent predictor of survival in lower-grade glioma(LGG), with a cox coefficient of 0.251 indicating a worse prognosis. Moreover, AIF1 expression was positively correlated with infiltrating levels of CD4+ T and B cells, macrophages, neutrophils, and DCs in LGG and glioblastoma(GBM). AIF1 expression also showed strong correlations with specific immune cell markers in LGG and GBM. In addition, AIF1 expression potentially contributed to the regulation of glioma-associated macrophages and microglia. In conclusion, our findings suggested that AIF1 was correlated with prognosis and immune infiltrating levels, and it can be used as a prognostic factor in gliomas.

Redox Regulator GLRX Is Associated With Tumor Immunity in Glioma.

Glutaredoxin is central to cellular redox chemistry and regulates redox homeostasis and malignant progression of many cancers. In glioma, the role of its coding gene (GLRX) remains unclear. We aimed to elucidate the role of glutaredoxin at the transcriptome level and its clinical prognostic value in glioma. In total, we evaluated 1,717 glioma samples with transcriptome data and corresponding clinical data as well as single-cell sequencing data from 6 glioma patients from publicly available databases. Gene set variation analysis and gene ontology analysis were performed to reveal the biological function of GLRX. The immune cell enrichment score was calculated by GSVA analysis. Single-cell sequencing data was visualized by t-distributed stochastic neighbor embedding analysis. The prognostic value of GLRX in glioma was verified by the Kaplan-Meier curve and multivariate COX analysis. GLRX was found to be highly enriched in gliomas of higher grades with wild-type IDH, without 1p/19q co-deletion, and with a methylated MGMT promoter. Moreover, GLRX could be a potential marker for the mesenchymal molecular subtype of gliomas. The expression of GLRX was closely related to the tumor immune process, immune checkpoints, and inflammatory factors with GLRX being specifically expressed in M0 macrophages. GLRX is also shown to be an independent prognostic factor in glioma. Altogether, our study outcomes show that GLRX is highly enriched in malignant gliomas and is closely related to the tumor immune microenvironment. Therefore, GLRX-targeted cell redox regulatory therapy may enhance the efficacy of glioma immunotherapy.

A nuclear transport-related gene signature combined with IDH mutation and 1p/19q codeletion better predicts the prognosis of glioma patients

BackgroundThe nuclear transport system has been proposed to be indispensable for cell proliferation and invasion in cancers. Prognostic biomarkers and molecular targets in nuclear transport systems have been developed. However, no systematic analysis of genes related to nuclear transport in gliomas has been performed. An integrated prognostic classification involving mutation and nuclear transport gene signatures has not yet been explored.MethodsIn the present study, we analyzed gliomas from a training cohort (TCGA dataset, n = 660) and validation cohort (CGGA dataset, n = 668) to develop a prognostic nuclear transport gene signature and generate an integrated classification system. Gene set enrichment analysis (GSEA) showed that glioblastoma (GBM) was mainly enriched in nuclear transport progress compared to lower-grade glioma (LGG). Then, we developed a nuclear transport risk score (NTRS) for gliomas with a training cohort. NTRS was significantly correlated with clinical and genetic characteristics, including grade, age, histology, IDH status and 1p/19q codeletion, in the training and validation cohorts.ResultsSurvival analysis revealed that patients with a higher NTRS exhibited shorter overall survival. NTRS showed better prognostic value compared to classical molecular markers, including IDH status and 1p/19q codeletion. Furthermore, univariate and multivariate analyses indicated that NTRS was an independent prognostic factor for gliomas. Enrichment map and Gene Ontology analysis demonstrated that signaling pathways related to the cell cycle were enriched in the NTRSHigh group. Subgroup survival analysis revealed that NTRS could differentiate the outcomes of low- and high-risk patients with wild-type IDH or mutant IDH and 1p/19q non-codeletion.ConclusionsNTRS is associated with poor outcomes and could be an independent prognostic marker in diffuse gliomas. Prognostic classification combined with IDH mutation, 1p/19q codeletion and NTRS could better predict the survival of glioma patients.

CircRNAs as potential biomarkers for the clinicopathology and prognosis of glioma patients: a meta-analysis

BackgroundAn increasing number of studies have reported circular RNAs (circRNAs) as new potential biomarkers for the prognosis of gliomas. However, the overall prognostic value of circRNAs for glioma remains unclear. Therefore, this study is the first comprehensive evaluation of the clinicopathological and prognostic value of dysregulated circRNAs in the treatment of glioma patients.MethodsWe systematically reviewed the online databases of PubMed, Web of Science, EMBASE, and Cochrane Library to identify studies that explored the relationship between circRNA expression and clinicopathological and prognostic factors in glioma through April 11, 2020. The quality of the included studies was evaluated by the Newcastle-Ottawa Scale (NOS) checklists. Clinicopathological features were assessed by pooled odds ratios (ORs) and 95% confidence intervals (CIs), and overall survival (OS) was assessed by hazard ratios (HRs) and 95% CIs.ResultsTwenty-four eligible studies, including 22 studies of clinicopathological features, 1 diagnostic study, and 18 studies of prognosis, that included a total of 1390 patients were ultimately included in this study. Meta-analysis showed that highly expressed oncogenic circRNAs were significantly related to poor clinicopathological features (age: P = 0.026; tumor size: P ≤ 0.001; tumor grade: P ≤ 0.001; KPS: P = 0.012) and worse overall survival (OS) (HR = 2.01, 95% CI: 1.61–2.50, P ≤ 0.001). Moreover, we found that highly expressed tumor-suppressor circRNAs were related to better clinicopathological features (gender: P = 0.042; age: P = 0.014; tumor size: P = 0.022; tumor grade: P ≤ 0.001) and longer OS (HR = 2.70, 95% CI: 1.82–3.99, P ≤ 0.001).ConclusionsIn conclusion, there is a significant correlation between the dysregulated expression of circRNAs and the clinicopathology and prognosis of glioma patients.

IFI30 expression is an independent unfavourable prognostic factor in glioma.

Gamma‐interferon‐inducible lysosomal thiol reductase, the only known lysosomal thiol reductase, is encoded by gene IFI30 and expressed constitutively in antigen‐presenting cells. Our comprehensive study on IFI30 in gliomas found its expression to be high in glioblastomas and in gliomas with a mesenchymal subtype or wild‐type isocitrate dehydrogenase, all of which indicated the malignancy and poor outcomes of gliomas. Kaplan‐Meier survival analysis ascertained that high IFI30 expression conferred poor outcomes. The IFI30 expression levels also showed high efficiency in predicting 1‐, 3‐ and 5‐year overall survival. Univariable and multivariable Cox regression analyses were performed to define IFI30 as an independent prognostic marker. Biological process analysis suggested that IFI30 was involved in immune responses. ESTIMATE and CIBERSORT were applied to evaluate immune cell infiltration, with results indicating that samples with higher IFI30 expression had higher infiltration of immune cells, including regulatory T cells and M0 macrophages. Correlation analysis showed that IFI30 was significantly positively correlated with immune checkpoints that suppress effective antitumour immune responses. Immunohistochemical staining was also performed to confirm the association between IFI30 expression and the immune phenotype. The suggested correlation between high IFI30 expression and an immunosuppressive phenotype contributes to our knowledge about the glioma microenvironment and might provide clues for the development of novel therapeutic targets.

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.

ABCC8 mRNA expression is an independent prognostic factor for glioma and can predict chemosensitivity

Glioma is the most common primary intracranial tumor and is associated with very low survival rates. The development of reliable biomarkers can help to elucidate the molecular mechanisms involved in glioma development. Here the expression of ABCC8 mRNA, clinical characteristics, and survival information based on 1893 glioma samples from four independent databases were analyzed. The expression patterns of ABCC8 mRNA were compared by a Chi square test. The overall survival rate of gliomas was evaluated according to the expression level of ABCC8 mRNA. The prognostic value of this marker in gliomas was tested using Cox single factor and multi factor regression analyses. We found patients with low WHO grade, oligodendrocytoma, low molecular grade, IDH mutation, and 1p19q combined deletion had high ABCC8 mRNA expression. The patients with high expression of ABCC8 mRNA had longer survival. ABCC8 mRNA expression was a new independent prognostic index for glioma. Temozolomide chemotherapy was an independent index to prolong overall survival in high ABCC8 mRNA expression glioma patients, whereas in patients with low expression, there was no significant difference. So ABCC8 mRNA expression could be an independent prognostic indicator for glioma patients and could predict the sensitivity of glioma to temozolomide.

Radiomics Features Predict CIC Mutation Status in Lower Grade Glioma.

MRI in combination with genomic markers are critical in the management of gliomas. Radiomics and radiogenomics analysis facilitate the quantitative assessment of tumor properties which can be used to model both molecular subtype and predict disease progression. In this work, we report on the Drosophila gene capicua (CIC) mutation biomarker effects alongside radiomics features on the predictive ability of CIC mutation status in lower-grade gliomas (LGG). Genomic data of lower grade glioma (LGG) patients from The Cancer Genome Atlas (TCGA) (n = 509) and corresponding MR images from TCIA (n = 120) were utilized. Following tumor segmentation, radiomics features were extracted from T1, T2, T2 Flair, and T1 contrast enhanced (CE) images. Lasso feature reduction was used to obtain the most important MR image features and then logistic regression used to predict CIC mutation status. In our study, CIC mutation rarely occurred in Astrocytoma but has a high probability of occurrence in Oligodendroglioma. The presence of CIC mutation was found to be associated with better survival of glioma patients (p < 1e−4, HR: 0.2445), even with co-occurrence of IDH mutation and 1p/19q co-deletion (p = 0.0362, HR: 0.3674). An eleven-feature model achieved glioma prediction accuracy of 94.2% (95% CI, 94.03–94.38%), a six-feature model achieved oligodendroglioma prediction accuracy of 92.3% (95% CI, 91.70–92.92%). MR imaging and its derived image of gliomas with CIC mutation appears more complex and non-uniform but are associated with lower malignancy. Our study identified CIC as a potential prognostic factor in glioma which has close associations with survival. MRI radiomic features could predict CIC mutation, and reflect less malignant manifestations such as milder necrosis and larger tumor volume in MRI and its derived images that could help clinical judgment.

Comprehensive analysis of potential prognostic biomarker in gliomas

PurposeGliomas are common intracranial tumors with the characteristic of diffuse and invasive growth. The prognosis is poor, and the recurrence rate and mortality are higher. With the development of big data technology, many methods such as natural language processing, computer vision and image processing have been deeply applied in the medical field. This can help clinicians to provide personalized and precise diagnosis and therapeutic schedule for patients with different type of gliomas to achieve the best therapeutic effect. The purpose of this paper is to summarize and extract useful information from published research results by conducting a secondary analysis of the literature.Design/methodology/approachThe PubMed and China National Knowledge Infrastructure (CNKI) literature database were used to retrieve published Chinese and English research papers about human gliomas. Comprehensive analysis was applied to conduct this research. The factors affecting survival and prognosis were screened and analyzed respectively in this paper, and different methods for multidimensional data of patients were discussed.FindingsThis paper identified biomarkers and therapeutic modalities associated with prognosis for different grade of gliomas. This paper investigated the relationship among these clinical prognostic factors and different histopathologic tying and grade of gliomas by comprehensive analysis. This paper summarizes the research progress of biomarker in medical imaging and genomics of gliomas to improve prognosis and the current status of treatment in China.Originality/valueCombined with multimodal data such as genomics data, medical image data and clinical information data, this paper comprehensively analyzed the prognostic factors of glioma and provided guidance and evidence for rational treatment planning and improvement of clinical treatment prognosis.

RSK4: a new prognostic factor in glioma

Glioma is the most common and fatal brain tumour and has a poor prognosis. Ribosomal S6 protein kinase 4 (RSK4) has been found to be involved in multiple tumour types; however, the role of RSK4 in gliomas and its clinical relevance remain unclear. In the present study, RSK4 expression was found to be significantly increased in glioma tissues compared with matched adjunct non-noncancerous tissues. Moreover, the expression of RSK4 was significantly higher in high-grade (III and IV) glioma tissues than in low-grade (I and II) glioma tissues. The data showed that the expression of RSK4 was significantly correlated with WHO grade, three-year survival rate and five-year survival rate. Kaplan-Meier analyses showed that patients with high RSK4 expression had poor overall survival. In addition, multivariate Cox regression analysis showed that RSK4 might be an independent prognostic factor in glioma patients. Collectively, these results suggest that RSK4 may be a new prognostic factor in glioma patients, and RSK4 is expected to be a potential biomarker and a potential target for glioma therapy.

Prognostic value of a nine-gene signature in glioma patients based on tumor-associated macrophages expression profiling

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.

Inflammation and lymphocyte infiltration are associated with shorter survival in patients with high-grade glioma

ABSTRACT Glioma represents a serious health burden in terms of morbidity and mortality. The prognostic significance of the lymphoid and myeloid infiltrates in glioma is not clearly determined. Moreover, the characterization of different leukocyte subsets in the tumor microenvironment relies mainly on immunohistochemistry observations, and data about their association with prognosis are contradictory. Here, we performed acomprehensive study of both the tumor-infiltrating and circulating immune compartments of patients with high-grade glioma. Nineteen tumor biopsies and 30 PBMC samples were analyzed by RNA sequencing. Validation was performed on The Cancer Genome Atlas (TCGA) RNA sequencing data from glioma and on additional 39 tumor biopsies analyzed by flow cytometry. We identified prognostic tumor and peripheral immune signatures, which associate increased inflammation, immune infiltration and activation with shorter overall survival in high-grade glioma patients. Importantly, we confirmed our observations by flow cytometry analysis and validated the tumor-signature using the TCGA dataset. In addition, both tumor genotype and grade associated with the degree of glioma immune infiltration. Unlike in the majority of cancers, lymphocyte infiltration at the tumor site is anegative prognostic factor in glioma, suggesting the ambivalent pro-tumorigenic role of immune responses in glioma.

Prognostic factor identification by analysis of the gene expression and DNA methylation data in glioma.

Objective: This study was aimed to identify prognostic factors in glioma by analysis of the gene expression and DNA methylation data. Methods: The RNAseq and DNA methylation data associated with glioma were downloaded from GEO and TCGA databases to analyze the differentially expressed genes (DEGs) and methylated genes between tumor and normal tissues. Function and pathway analyses, co-expression network and survival analysis were performed based on these DEGs. The intersection genes of DEGs and differentially methylated genes were obtained followed by function analysis. Results: Total 2190 DEGs were identified between tumor and normal tissues, which were significantly enriched in neuron differentiation associated functions, as well as ribosome pathway. There were 6186 methylation sites (2834 up-regulated and 3352 down-regulated) with significant differences in tumor vs. normal. In the constructed co-expression network, DPP6, MAPK10 and RPL3 were hub genes. Survival analysis of 20 DEGs obtained 18 prognostic genes, among which 9 were differentially methylated, such as LHFPL tetraspan subfamily member 3 (LHFPL3), cadherin 20 (CDH20), complexin 2 (CPLX2), and tenascin R (TNR). The intersection of DEGs and differentially methylated genes (632 genes) were significantly enriched in functions of neuron differentiation. Conclusion: DPP6, MAPK10 and RPL3 may play important roles in tumorigenesis of glioma. Additionally, methylation of LHFPL3, CDH20, CPLX2, and TNR may serve as prognostic factors of glioma.

Single-nucleus chromatin accessibility reveals intratumoral epigenetic heterogeneity in IDH1 mutant gliomas

The presence of genome-wide DNA hypermethylation is a hallmark of lower grade gliomas (LGG) with isocitrate dehydrogenase (IDH) mutations. Further molecular classification of IDH mutant gliomas is defined by the presence (IDHmut-codel) or absence (IDHmut-noncodel) of hemizygous codeletion of chromosome arms 1p and 19q. Despite the DNA hypermethylation seen in bulk tumors, intra-tumoral heterogeneity at the epigenetic level has not been thoroughly analyzed. To address this question, we performed the first epigenetic profiling of single cells in a cohort of 5 gliomas with IDH1 mutation using single nucleus Assay for Transposase-Accessible Chromatin with high-throughput sequencing (snATAC-seq). Using the Fluidigm HT IFC microfluidics platform, we generated chromatin accessibility maps from 336 individual nuclei, and identified variable promoter accessibility of non-coding RNAs in LGGs. Interestingly, local chromatin structures of several non-coding RNAs are significant factors that contribute to heterogeneity, and show increased promoter accessibility in IDHmut-noncodel samples. As an example for clinical significance of this result, we identify CYTOR as a poor prognosis factor in gliomas with IDH mutation. Open chromatin assay points to differential accessibility of non-coding RNAs as an important source of epigenetic heterogeneity within individual tumors and between molecular subgroups. Rare populations of nuclei that resemble either IDH mutant molecular group co-exist within IDHmut-noncodel and IDHmut-codel groups, and along with non-coding RNAs may be an important issue to consider for future studies, as they may help guide predict treatment response and relapse.A web-based explorer for the data is available at shiny.turcanlab.org.

Relationship between circulating inflammatory factors and glioma risk and prognosis: A meta-analysis.

BackgroundInflammatory factors have been considered a significant factor contributing to the development and progression of glioma. However, the relationship between circulating inflammatory factors and glioma risk as well as their prognostic values in glioma patients is still inconclusive. Here, we performed a meta‐analysis to address this issue.MethodsRelevant articles were identified through PubMed, EMBASE, the Cochrane Library, Web of Science, Wanfang database, and China National Knowledge Infrastructure (CNKI) from inception to February 2019. The weighted mean differences (WMDs) or standard mean differences (SMDs) with 95% confidence intervals (CIs) were used to describe the predictive ability of the levels of circulating inflammatory factors on glioma risk. To evaluate the prognostic values of the circulating inflammatory factors in glioma, hazard ratios (HRs) with 95% CIs were used.ResultsThirty‐one studies comprising 2587 patients were included. The overall analysis showed that increased circulating interleukin‐6 (IL‐6) [SMD 0.81 (95% CI: 0.21‐1.40; P = .008)], interleukin‐8 (IL‐8) [SMD 1.01 (95% CI: 0.17‐1.84; P = .018)], interleukin‐17 (IL‐17) [SMD 1.12 (95% CI: 0.26‐1.98; P = .011)], tumor necrosis factor‐α (TNF‐α) [SMD 1.80 (95% CI: 1.03‐2.56; P = .000)], transforming growth factor‐β (TGF‐β) [SMD 10.55 (95% CI: 5.59‐15.51; P = .000)], and C‐reactive protein (CRP) [SMD 0.95 (95% CI: 0.75‐1.15; P = .000)] levels were significantly associated with glioma risk. On the other hand, our results showed that circulating IL‐6 [HR 1.10 (95% CI: 1.05‐1.16; P = .000)] and CRP [HR 2.02 (95% CI: 1.52‐2.68; P = .000)] levels were highly correlated with a poor overall survival (OS) rate in glioma patients.ConclusionOur results indicate that increased circulating IL‐6, IL‐8, IL‐17, TNF‐α, TGF‐β, and CRP levels are significantly associated with increased glioma risk. Moreover, our meta‐analysis suggests that circulating IL‐6 and CRP may serve as powerful biomarkers for a poor prognosis in glioma patients.

The polymorphisms (rs3213801 and rs5744533) of DNA polymerase kappa gene are not related with glioma risk and prognosis: A case-control study.

DNA polymerase kappa (POLK), one of the specialized Y family DNA polymerases, functions in translesion synthesis and is suggested to be related with cancers. Single nucleotide polymorphisms (SNPs) in specialized DNA polymerases have been demonstrated to be associated with cancer risk. To evaluate the association of two common POLK variants (rs3213801 C>T and rs5744533 C>T) with glioma, we conducted a case‐control study and genotyped these two POLK variants in 605 patients and 1300 healthy controls. The association analysis revealed no significant correlations were observed between these two POLK SNPs and glioma risk. However, the POLK rs3213801 CT genotype was found to be higher in older glioma patients (≥40) than in younger patients (P = .026). Compared with patients harboring the CC genotype, the frequencies of POLK rs5744533 CT and CT+TT genotypes were increased in patients with lower World Health Organization (WHO) grade glioma (P = .028, 0.044, respectively). According to Kaplan‐Meier analysis and log‐rank tests, POLK SNPs were not correlated with either the overall survival or progression‐free survival. Nevertheless, multivariate analysis revealed that the age (≥40) could increase the risk of death in glioma patients (P < .05), while gross‐total resection and temozolomide treatment were found to play protective roles in glioma prognosis (P < .001, respectively). Overall, our results indicated that POLK variants rs3213801 and rs5744533 are not associated with glioma risk and prognosis. However, these polymorphisms are likely to be associated with certain glioma characteristics, such as age and WHO grade. The age, surgery types, and chemotherapy could be independent prognostic factors in glioma. More studies are required to confirm our findings.

Diagnostic and prognostic value of microRNA-193b in patients with glioma and its effect on tumor progression.

Emerging evidence has indicated the important roles of microRNAs (miRs) in the pathogenesis of cancer in humans. The present study sought to assess the expression patterns of miR-193b in patients with glioma, and investigated its clinical significance and biological function in this disease. The expression of miR-193b in the serum, tissues and cells of patients with glioma was analyzed using reverse transcription-quantitative PCR. Its diagnostic value was evaluated using the receiver operating characteristic (ROC) curve analysis, and its prognostic value was analyzed using Kaplan-Meier survival and Cox regression analyses. Experiments on glioma cells were conducted to explore the influence of miR-193b on proliferation, migration and invasion. Increased expression of miR-193b was observed in serum, tissues and cells of patients with glioma compared with the corresponding controls (all P<0.05). miR-193b expression was associated with the World Health Organization grading and the Karnofsky Performance Scale of the patients (all P<0.05). The area under the curve of the ROC analysis of miR-193b was 0.903, indicating its high diagnostic accuracy for glioma. High expression of miR-193b was associated with poor overall survival rate in patients (P=0.002). Therefore, miR-193b is a potential independent prognostic factor in glioma. Furthermore, the overexpression of this miR in glioma cells led to increased proliferation, migration and invasion, whereas its inhibition resulted in the opposite effects on these cell behaviors (all P<0.05). Thus, the findings from the present study indicate that the overexpression of miR-193b serves as a useful biomarker for the diagnosis and prediction of prognosis in glioma. The upregulation of miR-193b expression may enhance glioma progression, and may therefore be a potential target for glioma therapy.

Glioblastoma in the elderly

Incidence of malignant gliomas is growing in the elderly population. Unfortunately, increasing age is one of the most important negative prognostic factors in gliomas. However, the previous nihilistic approach is progressively changing towards more active strategies. Particularly, prospective randomized studies have recently established the benefit of radiotherapy associated with concomitant and adjuvant chemotherapy by temozolomide in older patients with good functional status suffering from malignant gliomas. Chemotherapy alone may even be useful in this population, especially in patients with poor functional status. Symptomatic treatments such as corticosteroids and antiepileptic drugs may be less tolerated in this population compared to younger patients and should be used only if needed. Initial performance status, quality of life and concomitant pathologies are obviously important factors to consider before treatment onset. The willingness of the patient and his caregivers will also be the key of the therapeutic decision. In the future, it will be necessary to develop specific schedules of treatment in this population. For this reason, prospective randomized clinical trials are needed to improve the pattern of care of malignant glioma in the elderly.

Low LINC00599 expression is a poor prognostic factor in glioma.

LINC00599 has been suggested to be involved in physiological and pathological processes including carcinogenesis. However, the clinical and prognostic significance of LINC00599 in glioma patients and the effect of LINC00599 on glioma cell migration and invasion remain unknown. In our results, we first observe the expression of LINC00599 in 31 types of human cancers including tumor tissues and corresponding normal tissues at The Cancer Genome Atlas (TCGA) database, and found that LINC00599 expression levels were only reduced in lower grade glioma (LGG) tissues and glioblastoma multiforme (GBM) tissues compared with normal brain tissues. Moreover, we confirmed levels of LINC00599 expression were decreased in glioma tissues and cell lines compared with matched adjacent normal tissues and normal human astrocytes (NHAs), respectively. Meanwhile, we found that glioma tissues with WHO III-IV grade exhibited lower levels of LINC00599 expression than glioma tissues with I-II grade. The survival analysis at TCGA data showed low LINC00599 expression was associated with poor disease-free survival and overall survival in glioma patients. In vitro study suggested up-regulation of LINC00599 depressed glioma cell migration and invasion through regulating epithelial–mesenchymal transition (EMT) process. In conclusion, LINC00599 acts as a tumor-suppressing long non-coding RNA (lncRNA) in glioma.

Peripheral blood test provides a practical method for glioma evaluation and prognosis prediction.

SummaryObjectiveTo investigate the relationship between tumor characteristics and the preoperative counts of immune cells in peripheral blood test in glioma patients.MethodsWe included 260 WHO grades II‐IV patients who had preoperative peripheral blood test result from Sanbo hospital as training set. The 66 patients from Tiantan hospital was obtained for validation. RNA sequencing data from CGGA and TCGA datasets were used to evaluate the features of neutrophil subtype and lymphocyte subtype in glioma.ResultsWe revealed that the count of preoperative lymphocytes, eosinophils and neutrophils were associated with glioma grades. Neutrophil‐to‐lymphocyte ratio (NLR) <3.2 was associated with better prognosis, whereas increased NLR was strongly corresponding with a poor prognosis. Lymphocyte type glioma patients demonstrated a positive correlation with isocitrate dehydrogenase (IDH) mutation and lower grade. IDH mutant glioma contained a higher proportion of tumor‐infiltrating lymphocytes than IDH wild‐type glioma. The immune subtype (neutrophil subtype and lymphocyte subtype) was an independent prognostic factor in glioma.ConclusionOur data demonstrated that NLR was an important prognostic factor in glioma. We classified that the immune subtype of glioma may contribute to a better understanding of disease pathogenesis and lead to the identification of new therapeutic targets for glioma patients.