Prognostic Factor In Glioma Research Articles

P96-8 C-reactive protein as prognostic factor in glioma: a systematic review and meta-analysis

P96-8 C-reactive protein as prognostic factor in glioma: a systematic review and meta-analysis

Hypoxia-related THBD+ macrophages as a prognostic factor in glioma: Construction of a powerful risk model.

Glioma is a prevalent malignant tumour characterized by hypoxia as a pivotal factor in its progression. This study aims to investigate the impact of the most severely hypoxic cell subpopulation in glioma. Our findings reveal that the THBD+ macrophage subpopulation is closely associated with hypoxia in glioma, exhibiting significantly higher infiltration in tumours compared to non-tumour tissues. Moreover, a high proportion of THBD+ cells correlates with poor prognosis in glioblastoma (GBM) patients. Notably, THBD+ macrophages exhibit hypoxic characteristics and epithelial-mesenchymal transition features. Silencing THBD expression leads to a notable reduction in the proliferation and metastasis of glioma cells. Furthermore, we developed a THBD+ macrophage-related risk signature (THBDMRS) through machine learning techniques. THBDMRS emerges as an independent prognostic factor for GBM patients with a substantial prognostic impact. By comparing THBDMRS with 119 established prognostic features, we demonstrate the superior prognostic performance of THBDMRS. Additionally, THBDMRS is associated with glioma metastasis and extracellular matrix remodelling. In conclusion, hypoxia-related THBD+ macrophages play a pivotal role in glioma pathogenesis, and THBDMRS emerges as a potent and promising prognostic tool for GBM, contributing to enhanced patient survival outcomes.

LncRNA CAI2 Contributes to Poor Prognosis of Glioma through the PI3K-Akt Signaling Pathway.

We aim to explore new potential therapeutic targets and markers in human glioma. Gliomas are the most common malignant primary tumor in the brain. In the present research, we evaluated the effect of CAI2, a long non-coding RNA, on the biological behaviors of glioma and explored the related molecular mechanism. The expression of CAI2 was analyzed using qRT-PCR in 65 cases of glioma patients. The cell proliferation was determined with MTT and colony formation assays, and the PI3K-AKt signaling pathway was analyzed using western blot. CAI2 was upregulated in human glioma tissue compared with the matched, adjacent nontumor tissue and was correlated with WHO grade. Survival analyses proved that the overall survival of patients with high CAI2 expression was poor compared to that of patients with low CAI2 expression. High CAI2 expression was an independent prognostic factor in glioma. The absorbance values in the MTT assay after 96 h were .712 ± .031 for the si-control and .465 ± .018 for the si- CAI2-transfected cells, and si-CAI2 inhibited colony formation in U251 cells by approximately 80%. The levels of PI3K, p-AKt, and AKt in si-CAI2-treated cells were decreased. CAI2 may promote glioma growth through the PI3K-AKt signaling pathway. This research provided a novel potential diagnostic marker for human glioma.

The significance of miR-124 in the diagnosis and prognosis of glioma: A systematic review.

Glioma is a type of cancer that affects the central nervous system and necessitates a non-invasive diagnostic and prognostic assessment. MicroRNAs (miRNAs) play a crucial role in glioma and can provide valuable information about the prognosis of patients with this condition. MiR-124 is associated with molecules that play crucial roles in cellular processes, and any disruption in its expression can have a detrimental effect on cells, potentially leading to cancer. Therefore, miR-124 can be a valuable biomarker for diagnosis and prognosis in glioma. This review aims to highlight the role of miR-124 as a diagnostic and prognostic factor in glioma. To address this issue, we systemically reviewed and used various search strategies across three databases (PubMed, Web of Science and Scopus) and then yielded 3046 records from inception to September 2023. Records that did not meet our inclusion criteria were excluded. Following the screening process, our analysis included and summarized 13 eligible studies that not only measured miR-124 in serum, plasma, and tissue of glioma patients but also provided insights intomiR-124 as a prognostic and diagnostic biomarker. Thirteen studies were included for diagnostic accuracy, and five were considered for prognostic importance of miR-124. Based on our results, a single study showed an increase in miR-124 levels in exosomes obtained from patient serum, whereas the data from the 12 studies analyzed consistently pointed towards a reduction in miR-124 levels in various glioma samples. In conclusion, our findings suggest that miR-124 may be a useful diagnostic and prognostic biomarker in glioma. However, further investigations are required to draw more definitive conclusions.

CSF3R as a potential prognostic biomarker and immunotherapy target in glioma.

Gliomas are the most common malignant brain tumors, with complicated etiology and poor prognosis. However, there is still a lack of specific biomarkers for the diagnosis, treatment and prognosis assessment for glioma patients. Hence, the purpose of this study was to screen biomarkers for prognostic assessment and therapeutic interventions in gliomas. We utilized The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases to investigate the role of colony-stimulating factor 3 receptor (CSF3R) in glioma. Data analysis was conducted using R, GEPIA 2, TISCH and DepMap. CSF3R was up-regulated in glioma and associated with the clinical pathological features of the patients. Kaplan-Meier survival analysis indicated a significant association between the expression of CSF3R and prognosis in patients. Univariate and multivariate Cox analyses revealed that patients with high expression of CSF3R have a worse prognosis, and the expression of CSF3R was an independent prognostic factor in gliomas. The nomogram constructed based on the expression of CSF3R demonstrated lower 1-, 3-, and 5-year overall survival (OS) in patients with high CSF3R expression. The biological functional analysis of CSF3R demonstrated its association with various immune regulatory signals. Furthermore, CSF3R was linked to the expression of immune checkpoints and resistance to immunotherapy. Notably, CSF3R was predominantly detected in monocytes/macrophages. Our study suggested that CSF3R might potentially function as an independent prognostic factor for glioma and hold promise as a biomarker and target for immunotherapy in glioma.

MrGPS: an m6A-related gene pair signature to predict the prognosis and immunological impact of glioma patients.

N6-methyladenosine (m6A) RNA methylation is the predominant epigenetic modification for mRNAs that regulates various cancer-related pathways. However, the prognostic significance of m6A modification regulators remains unclear in glioma. By integrating the TCGA lower-grade glioma (LGG) and glioblastoma multiforme (GBM) gene expression data, we demonstrated that both the m6A regulators and m6A-target genes were associated with glioma prognosis and activated various cancer-related pathways. Then, we paired m6A regulators and their target genes as m6A-related gene pairs (MGPs) using the iPAGE algorithm, among which 122 MGPs were significantly reversed in expression between LGG and GBM. Subsequently, we employed LASSO Cox regression analysis to construct an MGP signature (MrGPS) to evaluate glioma prognosis. MrGPS was independently validated in CGGA and GEO glioma cohorts with high accuracy in predicting overall survival. The average area under the receiver operating characteristic curve (AUC) at 1-, 3- and 5-year intervals were 0.752, 0.853 and 0.831, respectively. Combining clinical factors of age and radiotherapy, the AUC of MrGPS was much improved to around 0.90. Furthermore, CIBERSORT and TIDE algorithms revealed that MrGPS is indicative for the immune infiltration level and the response to immune checkpoint inhibitor therapy in glioma patients. In conclusion, our study demonstrated that m6A methylation is a prognostic factor for glioma and the developed prognostic model MrGPS holds potential as a valuable tool for enhancing patient management and facilitating accurate prognosis assessment in cases of glioma.

Expression of intra-tumoral necrosis-associated cytokine pattern correlated with prognosis and immune status in glioma.

Intra-tumoral necrosis (ITN) is reported to be an independent prognostic factor in glioma. However, knowledge of ITN is mainly limited to pseudopalisadwe, while its other aspects were neglected. Therefore, a deeper understanding of ITN could be valuable for understanding its exact role in glioma. The only reliable ITN model was time-dependently achieved with the GL261 syngeneic mouse model. The ITN-associated expression pattern was enriched from RNA sequencing. TCGA glioma samples were clustered into a high-expression group (HEG) and a low-expression group (LEG) based on their pattern and their association with prognosis, clinical status, immune status, and therapeutic responsiveness were compared. Mouse glioma with ITN demonstrated invasive histology. Cytokine signaling was significantly enriched in necrotic mouse glioma compared with non-necrotic glioma tissues. Nine pro-inflammatory (IL6, PPBP, IL1A, TNFSF11, CXCL11, CXCL9, CXCL10, CXCL3, and CCL8) and two anti-inflammatory cytokine (IL1RN and IL10) genes were found to be related to ITN-associated cytokine patterns. Comparative analysis showed that HEG had a significantly shorter survival time, five differentially distributed clinical statuses, more infiltrated immune cells, greater expression of immune checkpoints, and better therapeutic responsiveness than LEG. In conclusion, the ITN-associated cytokine pattern is characteristically expressed in glioma with ITN and might indicate necrosis missed in histology diagnosis. Its expression pattern could predict the prognosis, tumor grade, immune status, and therapeutic responsiveness of glioma patients.

RARRES2 is Downregulated in Isocitrate Dehydrogenase 1 Mutant Glioma Patients and Served as an Unfavorable Prognostic Factor of Glioma

Mutations in isocitrate dehydrogenase 1 (IDH1) induce extensive transcriptional alterations to promote glioma development. However, IDH1 mutation contributes the better clinical outcomes of glioma. Further understanding the transcriptional and DNA methylation changes mediated by IDH1 mutation will provide new therapeutic targets for glioma. Public glioma cohorts were collected and processed using R software. The transcriptional changes mediated by IDH1 mutation were determined and presented using heatmap. The differentially expressed genes in IDH1 mutant glioma were overlapped using TBtools. The prognostic effects of IDH1 regulated genes were determined by Kaplan-Meier survival analysis. Retinoic acid receptor responder 2 (RARRES2) was upregulated in IDH1 wild type lower-grade glioma (LGG) patients, and higher expression levels of RARRES2 were associated with worse clinical outcomes of LGG. Moreover, IDH1 wild type LGG patients with higher expression levels of RARRES2 had even worse overall survival. Compared with LGG, RARRES2 was upregulated in grade IV glioma (glioblastoma multiforme, GBM). Also, RARRES2 represented an unfavorable prognostic factor of glioma. In GBM, RARRES2 was also associated with IDH1 mutation. In both LGG and GBM, IDH1 mutation induced extensive DNA hypermethylation, and more than half genes that were downregulated in IDH1 mutant glioma were contributed by DNA hypermethylation. RARRES2 was also hypermethylated in IDH1 mutant LGG or GBM patients. Furthermore, RARRES2 hypomethylation was an unfavorable prognostic factor in patients with LGG. RARRES2 was downregulated by IDH1 mutation and served as an unfavorable prognostic factor in glioma.

MAPK9 is Correlated with a Poor Prognosis and Tumor Progression in Glioma

Glioma has a high incidence in young and middle-aged adults and a poor prognosis. Because of late diagnosis and uncontrollable recurrence of the primary tumor after failure of existing treatments, glioma patients tend to have a poor prognosis. Recent advances in research have revealed that gliomas exhibit unique genetic features. Mitogen-activated protein kinase 9 (MAPK9) is significantly upregulated in mesenchymal glioma spheres and may be a new target for glioma diagnosis. This study aimed to investigate the potential diagnostic significance and predictive value of MAPK9 in glioma. Paraffin-embedded tumor tissues and paracancerous tissues were collected from 150 glioma patients seen at the General Hospital of Northern Theater Command. Immunohistochemistry and western blot assays were used to detect the expression levels of MAPK9. Prognosis and survival analyses were performed using SPSS 26 software for univariate/multivariate analysis and log-rank analysis. Cellular models were used to assess the effect of MAPK9 overexpression and knockdown in vitro. MAPK9 expression was higher in glioma tissues than in paraneoplastic tissues. Prognostic and survival analyses revealed that the MAPK9 expression level is an independent prognostic factor in glioma patients. In addition, overexpression of MAPK9 significantly promoted the proliferation and migration of primary glioma cells, possibly via the Wnt/β-catenin-regulated EMT pathway. MAPK9 is an independent prognostic factor in glioma and is involved in tumor progression.

TREM2 is associated with tumor immunity and implies poor prognosis in glioma.

Triggering receptor expressed on myeloid cells 2 (TREM2) is expressed in myeloid cells of the central nervous system (CNS), which mediate the immunological response in a variety of diseases. Uncertain is the function of TREM2 in glioma and tumor immune responses. In this research, the expression patterns of TREM2 in glioma were analyzed, along with its prognostic value and functional roles. TREM2 expression is increased in glioblastomas, gliomas with a mesenchymal subtype, gliomas with wild-type isocitrate dehydrogenase, and gliomas without 1p/19q deletion, all of which suggest the aggressiveness and poor prognosis of gliomas. Gene ontology, KEGG, and Gene set variation analyses indicated that TREM2 may serve as an immune response mediator. However, the function of T cells against tumor cells was negatively correlated with TREM2, suggesting that TREM2 may suppress tumor immunity. Further investigation demonstrated a correlation between TREM2 expression and immune checkpoint expression. CIBERSORT research revealed a link between a higher TREM2 expression level and the enrichment of tumor-associated macrophages, especially M2 subtype. Single-cell analysis and multiple immunohistochemical staining results showed that microglia and macrophage cells expressed TREM2. Immunofluorescent staining indicated that knocking down the expression of TREM2 would result in a decrease in M2 polarization. TREM2 was discovered to be an independent prognostic factor in glioma. In conclusion, our findings revealed that TREM2 was significantly expressed in microglia and macrophage cells and was intimately associated with the tumor immune microenvironment. Thus, it is expected that small-molecule medications targeting TREM2 or monoclonal antibodies would enhance the efficacy of glioma immunotherapy.

Identification of therapeutic targets and prognostic biomarkers among frizzled family genes in glioma.

Background: The biological functions of the Frizzled gene family (FZDs), as the key node of wingless-type MMTV integration site family (Wnt) and mammalian target of rapamycin signaling pathways, have not been fully elucidated in glioma. This study aims to identify novel therapeutic targets and prognostic biomarkers for gliomas, which may help us understand the role of FZDs. Methods: RNA-sequence data were downloaded from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) projects. Survival analyses, Cox regression analyses, nomograms, calibration curves, receiver operating characteristic (ROC) curves, gene function enrichment analyses, and immune cell infiltration analyses were conducted using R. Results: High expressions of FZDs were positively associated with the activation of mTOR signaling. FZD1/2/3/4/5/7/8 was significantly highly expressed in tumor tissues, and the high expression of FZD1/2/5/6/7/8 was significantly positively associated with poorer prognosis. FZD2 and FZD6 positively served as independent predictors of poor prognosis. Gene function analysis showed that FZDs were associated with mTOR signaling, immune response, cytokine-cytokine receptor interaction, extracellular matrix organization, apoptosis, and p53 signaling pathway. Conclusions: Our finding strongly indicated a crucial role of FZDs in glioma. FZD1/2/5/6/7/8 could be an unfavorable prognostic factor in glioma and FZD2 and FZD6 may be novel independent predictors of poor prognosis in glioma.

Purine metabolism-related gene expression signature predicts survival outcome and indicates immune microenvironment profile of gliomas.

Glioma is the most common malignant tumor in the central nervous system. The impact of metabolism on cancer development and the immune microenvironment landscape has recently gained broad attention. Purines are involved in multiple metabolic pathways. It has been proved that purine metabolism could regulate malignant biological behaviors and response to immune checkpoint inhibitors in multiple cancers. However, the relationship of purine metabolism with clinicopathological features and the immune landscape of glioma remains unclear. In this study, we explored the relationships between the expression of purine metabolism-related genes (PuMGs) and tumor features, including prognosis and microenvironment of glioma, based on analyses of 1,523 tumors from 4 public databases and our cohort. Consensus clustering based on 136 PuMGs classified the glioma patients into two clusters with significantly distinguished prognosis and immune microenvironment landscapes. Increased immune infiltration was associated with more aggressive gliomas. The prognostic Purine Metabolism-Related Genes Risk Signature (PuMRS), based on 11 critical PuMGs, stratified the patients into PuMRS low- and high-risk groups in the training set and was validated by validation sets from multiple cohorts. The high-risk group presented with significantly shorter overall survival, and further survival analysis demonstrated that the PuMRS was an independent prognostic factor in glioma. The nomogram combining PuMRS and other clinicopathological factors showed satisfactory accuracy in predicting glioma patients' prognosis. Furthermore, analyses of the tumor immune microenvironment suggested that higher PuMRS was correlated with increased immune cell infiltration and gene expression signatures of "hotˮ tumors. Gliomas in the PuMRS high-risk group presented a higher expression level of multiple immune checkpoints, including PD-1 and PD-L1, and a better-predicted therapy response to immune checkpoint inhibitors. In conclusion, our study elucidated the relationship between the expression level of PuMGs and the aggressiveness of gliomas. Our study also endorsed the application of PuMRS to construct a new robust model for the prognosis evaluation of glioma patients. The correlations between the profiles of PuMGs expression and tumor immune microenvironment potentially provided guidance for immunotherapy in glioma.

Prognosis prediction and tumor immune microenvironment characterization based on tryptophan metabolism-related genes signature in brain glioma.

Glioma is the most common malignant tumor in the central nervous system with no significant therapeutic breakthrough in recent years. Most attempts to apply immunotherapy in glioma have failed. Tryptophan and its metabolism can regulate malignant features of cancers and reshape immune microenvironment of tumors. However, the role of tryptophan metabolism in glioma remains unclear. In current study, we explored the relationships between the expression pattern of tryptophan metabolism-related genes (TrMGs) and tumor characteristics, including prognosis and tumor microenvironment of gliomas through analyzing 1,523 patients' samples from multiple public databases and our own cohort. Based on expression of TrMGs, K-means clustering analysis stratified all glioma patients into two clusters with significantly different TrMG expression patterns, clinicopathological features and immune microenvironment. Furthermore, we constructed a tryptophan metabolism-related genes signature (TrMRS) based on seven essential TrMGs to classify the patients into TrMRS low- and high-risk groups and validated the prognostic value of the TrMRS in multiple cohorts. Higher TrMRS represented for potentially more active tryptophan catabolism, which could subsequently lead to less tryptophan in tumor. The TrMRS high-risk group presented with shorter overall survival, and further analysis confirmed TrMRS as an independent prognostic factor in gliomas. The nomograms uniting TrMRS with other prognostic factors manifested with satisfactory efficacy in predicting the prognosis of glioma patients. Additionally, analyses of tumor immune landscapes demonstrated that higher TrMRS was correlated with more immune cell infiltration and "hot" immunological phenotype. TrMRS was also demonstrated to be positively correlated with the expression of multiple immunotherapy targets, including PD1 and PD-L1. Finally, the TrMRS high-risk group manifested better predicted response to immune checkpoint inhibitors. In conclusion, our study illustrated the relationships between expression pattern of TrMGs and characteristics of gliomas, and presented a novel model based on TrMRS for prognosis prediction in glioma patients. The association between TrMRS and tumor immune microenvironment of gliomas indicated an important role of tryptophan and its metabolism in reshaping immune landscape and the potential ability to guide the application of immunotherapy for gliomas.

Abstract 3853: Investigating PRL2/PTP4A2 as a new target for glioblastoma treatment

Abstract Glioblastoma (GBM) is the most aggressive primary brain tumor. The standard treatment consists in tumor resection followed by chemo- and radio- therapy. However, tumor recurrence still remains inevitable, and the average lifespan of patients is only 15 months. Over the past decades, targeted therapies such as anti-angiogenic therapy, were proposed but failed to improve overall survival. In this context, the identification of new therapeutic targets is fundamental to implement current treatments. Protein Tyrosine Phosphatases (PTPs) are known to be involved in oncogenesis in several types of cancer, including GBM. Oncogenic properties of PRL2 has been demonstrated in different tumors (e.g. leukemia, breast, lung and nasopharyngeal cancer), but no evidence of PRL2 involvement in GBM has been reported so far. The aim of this project is to understand the role of PRL2 in GBM development, in order to evaluate the potential of PRL2 inhibition as a new therapeutic strategy. Analysis of TCGA (The Cancer Genome Atlas) dataset revealed that PRL2 was a poor prognostic factor in gliomas, and its expression correlated GBM aggressiveness. PTP4A2 expression also correlated with expression of genes involved in immune responses, reactive oxygen species, actin cytoskeleton and trafficking. Thus, we oriented our work towards these directions. To study PRL2 effects both in brain tumor cells and microenvironment, we used spheroids of patient-derived GBM cells, in which PTP4A2 expression was modulated. In vitro assays showed that migration, invasion and adhesion abilities were increased in PTP4A2-KO cells but cell proliferation was not affected. Next, in orthotopic xenografts experiments, PRL2 over-expression promoted tumor growth and reduced mouse survival rate. In addition, to overcome PRLs functional compensation and to use a clinically relevant strategy, we targeted all PRLs (PRL1, 2 and 3) activity with an inhibitory compound. Inhibiting all PRLs drastically reduced viability of GBM cells. Our project aims at discovering how PRL2 is involved in the progression and tumor microenvironment of GBM. Our results indicate that PRL2 promotes GBM growth in response to microenvironmental pressure and its inhibition improves mouse outcomes. However, the precise mechanisms of this regulation are still under investigation. Targeting PRLs and particularly PRL2 open avenue for therapeutic strategy in GBM treatment. Citation Format: Tiffanie Chouleur, Marie-Alix Derieppe, Wilfried Souleyreau, Michel L. Tremblay, Andreas Bikfalvi. Investigating PRL2/PTP4A2 as a new target for glioblastoma treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3853.

Procollagen C-protease enhancer protein is a prognostic factor for glioma and promotes glioma development by regulating multiple tumor-related pathways and immune microenvironment.

ObjectivesGlioma is a common type of brain tumor with high incidence and mortality rates. Procollagen C-protease enhancer protein (PCOLCE) has been shown to regulate tumor growth and metastasis in several cancers. However, the role of PCOLCE in glioma is unknown. This study aims to assess the association between PCOLCE and prognosis of glioma, and investigated the potential mechanisms.MethodsThe prognostic value of PCOLCE was determined using data from nine publicly available glioma cohorts. We also investigated the relationship between PCOLCE and glioma immune microenvironment and predicted response to immunotherapy based on the expression levels of PCOLCE. The potential roles of PCOLCE in glioma were also explored and validated in cell experiment.ResultsSurvival analysis suggested that high-PCOLCE expression was associated with poor prognosis in glioma. Upregulation of PCOLCE enhanced an immune suppressive microenvironment in glioma by regulating immunocyte infiltration and Cancer-Immunity Cycle. Cox and ROC analysis revealed that PCOLCE was a prognostic factor for glioma and could be used to predict survival of the patients. Patients with low-PCOLCE expression were more likely to respond to Immunotherapy with ICI (immune checkpoint inhibitor) and survive longer. Enrichment analysis showed that PCOLCE was associated with multiple tumor-related pathways. Finally, we demonstrated that the knockdown of PCOLCE inhibited glioma development by regulating cell cycle and promoting apoptosis in in vitro experiments.ConclusionPCOLCE promotes glioma progression by regulating multiple tumor-related pathways and immune microenvironment and can be used as a prognostic factor for glioma.

CLCF1 Is a Novel Potential Immune-Related Target With Predictive Value for Prognosis and Immunotherapy Response in Glioma.

BackgroundCardiotrophin-like cytokine factor 1 (CLCF1) has been described as an oncogene and a potential therapeutic target in a variety of cancers, but its role in glioma remains unknown.MethodsBased on The Cancer Genome Atlas (TCGA), we conducted a bioinformatics analysis to investigate the clinical significance and biological functions of CLCF1 in glioma at the transcriptional level and predicted the response to immunotherapy of glioma patients with different CLCF1 expression levels. All the results were further verified in Chinese Glioma Genome Altas(CGGA) Data processing and figure generating were performed with R language.ResultsElevated CLCF1 expression was common in cancers and usually predicted poor prognosis, which was also consistent with gliomas. In Univariate Cox Regression analysis and Kaplan-Meier survival analysis, tumor patients with higher CLCF1 expression tended to experience a worse prognosis. In the multivariate Cox proportional hazard model, the expression of CLCF1 was an independent prognostic factor in gliomas. The biological function analysis of CLCF1 in glioma showed that CLCF1 was closely associated with immune signatures, including immune-related pathways, immune cell infiltration, and immune checkpoints. Moreover, glioma patients with low CLCF1 expression showed a greater tendency to respond to anti-PD1/PD-L1 immunotherapy, indicating CLCF1 also had potential clinical significance in guiding immunotherapy. And CLCF1 as a member of the IL6 family had a better predictive value for prognosis and immunotherapy response in glioma than that of IL6 and other IL6 family members.ConclusionCLCF1 expression is an independent prognosticator and a promising therapeutic target correlated with immunotherapy in glioma.

Long non-coding RNA LINC01128 affects proliferation, migration, and invasion of glioma cells by regulating miR-27b-3p.

Glioma is a collective term for tumors derived from glial cells and neuronal cells in the nervous system, and is the most common malignant tumor in the brain. Nowadays, the problem of poor treatment effect and high recurrence rate of patients remains to be solved. In this study, the expression levels of LINC01128 in glioma tissues, cells, and normal control group were determined by real-time quantitative PCR (RT-qPCR). Kaplan-Meier curve was used to evaluate the prognosis and survival. Multivariate Cox analysis was chosen to estimate the prognostic risk factors of glioma. Cell counting kit-8 (CCK-8) and Transwell methods were used to detect the effect of silencing LINC01128 on the proliferation, migration, and invasion of glioma cells, and the targeting effect of LINC01128 on miR-27b-3p was determined based on bio-informatics analysis and luciferase activity detection. LINC01128 was up-regulated in glioma tissues and cells. The possibility of LINC01128 as a prognostic factor of glioma was obtained through Kaplan-Meier's clinical data analysis and multivariate Cox analysis. Silencing LINC01128 targeting miR-27b-3p inhibited the proliferation, migration, and invasion activity of glioma cells. Moreover, there was a negative correlation between LINC01128 and miR-27b-3p. Silencing LINC01128 inhibited the proliferation, migration, and invasion levels of glioma cells by targeting miR-27b-3p, thereby affecting the progression of gliomas.

GLIS family zinc finger 3 promoting cell malignant behaviors and NF-κB signaling in glioma

Glioma is a common tumor in the human central nervous system. However, its molecular mechanism in the pathogenesis and regulation of glioma progression is still unclear. In this study, we found that GLIS3 was up-regulated in glioma tissues, and the increased expression is positively correlated with advanced tumor grade. Survival evaluation disclosed that patients with high expression levels of GLIS3 normally have a poor prognosis. Functional analysis revealed the oncogenic role of GLIS3 in the development of glioma. GLIS3 promotes glioma cells’ invasion, migration, and proliferation. Meanwhile, deficiency of GLIS3 produces an inhibitory function upon NF-κB signaling pathway. This work demonstrated that GLIS3, acting as a target and prognostic factor for glioma, may promote the invasion, migration and proliferation of glioma cells involved in regulation of NF-κB signaling pathway.

Synthesis of [1-13 C-5-12 C]-alpha-ketoglutarate enables noninvasive detection of 2-hydroxyglutarate.

Isocitrate dehydrogenase 1 (IDH1) mutations that generate the oncometabolite 2-hydroxyglutarate (2-HG) from α-ketoglutarate (α-KG) have been identified in many types of tumors and are an important prognostic factor in gliomas. 2-HG production can be determined by hyperpolarized carbon-13 magnetic resonance spectroscopy (HP-13 C-MRS) using [1-13 C]-α-KG as a probe, but peak contamination from naturally occurring [5-13 C]-α-KG overlaps with the [1-13 C]-2-HG peak. Via a newly developed oxidative-Stetter reaction, [1-13 C-5-12 C]-α-KG was synthesized. α-KG metabolism was measured via HP-13 C-MRS using [1-13 C-5-12 C]-α-KG as a probe. [1-13 C-5-12 C]-α-KG was synthesized in high yields, and successfully eliminated the signal from C5 of α-KG in the HP-13 C-MRS spectra. In HCT116 IDH1 R132H cells, [1-13 C-5-12 C]-α-KG allowed for unimpeded detection of [1-13 C]-2-HG. 12 C-enrichment represents a novel method to circumvent spectral overlap, and [1-13 C-5-12 C]-α-KG shows promise as a probe to study IDH1 mutant tumors and α-KG metabolism.

A prognostic model based on CGGA and TCGA databases for predicting outcome of glioma patients.

e14017 Background: Glioma is the most frequent primary malignance of the central nervous system (CNS) and causes the top-ten deaths of cancers. Isocitrate dehydrogenase ( IDH) mutations and chromosome 1p and 19q codeletion are the known prognostic factors of glioma. However, it is still not enough to predict the outcomes. Herein, we conduct a prognostic model of patients with gliomas. Methods: The Chinese Glioma Genome Atlas (CGGA) contained 286 patients with whole-exome sequencing (WES) was used to established the model. Kaplan-Meier analysis based on log-rank test was used to confirm the single mutation overall survival (OS) factors (allele frequency≥ 5) in CGGA. The model was established based on the Cox regression of above significant factors. The data of 1122 patients with glioma in TCGA (The Cancer Genome Atlas) was used to validate the model. Results: According to the CGGA database, the OS factors of glioma patients were 1p/19q, CIC, EGFR ( p< 0.001), IDH1, IRS2, NF1, NOTCH1, PDGFRA, PTEN, ROS1, SMARCA4 and TP53. The Cox regression revealed 1p/19q codeletion (HR = 2.008, 95%CI 1.397-2.885, p< 0.001), EGFR (HR = 0.420, 95%CI 0.217-0.811, p= 0.010), PDGFRA (HR = 0.271, 95%CI 0.139-0.528, p< 0.001), and ROS1 (HR = 0.197, 95%CI 0.071-0.549, p= 0.002). Based on the β value of the regression equation, we divided the glioma patients into 3 groups (G1: harboring EGFR, PDGFR and/or ROS1 mutations; G2: wide type; G3: harboring 1p/19q without mutations in three genes). In TCGA, the OS of glioma patients was also showed G1 < G2 < G3 significantly. Conclusions: The prognostic model was divided glioma patients into three groups reasonably and could provide new reference for the glioma management. It needed to be further verified in more cohorts.