Factor In Glioma Research Articles

Increased expression of HBXIP (LAMTOR5) predicts poor prognosis and is correlated with immune-cell infiltration in glioma.

The poor response of patients with gliomas to existing immunotherapy has resulted in negligible improvement in prognosis. It is widely acknowledged that HBXIP serves as a transcriptional activator implicated in tumorigenesis across various cancer types. However, its specific role within glioma remains unclear. The aim of this study was to determine the association between HBXIP expression and survival and tumor-infiltrating immune cells. In addition, to construct a prognostic model to predict the overall survival (OS) of patients with glioma. Transcriptome sequencing data of 325 patients with glioma in the Chinese Glioma Genome Atlas (CGGA) database and 702 patients with glioma in The Cancer Genome Atlas (TCGA) were included for retrospective analysis and were used as the training group and the validation group, respectively. The expression of HBXIP in pancancer was detected in the database. A t-test and one-way analysis of variance were used to determine the differential expression levels of HBXIP across distinct subgroups of glioma. Functional annotations pertaining specifically to HBXIP's biological relevance underwent scrutiny via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The prognostic significance of HBXIP in glioma was ascertained through Kaplan-Meier curves and Cox regression models, a nomogram was used to establish a prognostic model, and the predictive power was evaluated with calibration curves and the concordance index. HBXIP's association with inhibitory immune checkpoints and tumor immune cell infiltration was examined using Pearson correlation coefficients via Tumor Immune Estimation Resource database. We found that HBXIP was upregulated in glioma, and that elevated HBXIP expression correlated significantly with adverse clinicopathological features and decreased OS. Multivariate analysis showed that HBXIP was an independent prognostic biomarker for glioma, and the established prognostic model could accurately predict the OS of patients. We also found that HBXIP expression was positively correlated with inhibitory immune checkpoint expression, HBXIP overexpression was associated with increased levels of tumor immunoinfiltrating cells in glioma that resulted in poor survival, and HBXIP demonstrated a positive correlation with the expression of immune cell marker genes. HBXIP is closely related to the clinicopathologic factors in glioma and may function as an oncogene. Its high expression is associated with poor prognosis, which may potentially be linked to immune escape and immune cell infiltration. HBXIP is a potential biomarker of prognostic and immune infiltration in glioma.

A reactive oxygen species-related signature predicts the prognosis and immunosuppressive microenvironment in gliomas

ABSTRACT Objective: Intracellular redox homeostasis is crucial for a series of physiological processes. Reactive oxygen species (ROS) play important roles in redox processes. ROS can maintain cell reproduction and survival at moderate levels while promoting the initiation and progression of tumors at high levels. Methods: Based on a comprehensive analysis of ROS-related gene expression profiles, we established a gene signature associated with ROS to explore its influence on prognosis and immune microenvironment in gliomas. Results: The ROS-related gene expression profile dichotomized patients into two groups with different clinicopathological features and prognoses. A 19-gene ROS-related signature was used to robustly predict prognosis in both training and validation datasets. Functional analysis indicated an association between ROS levels and the immune microenvironment. The expression of immune checkpoints and M2-type markers was upregulated in the high-risk group, which suggested the immunosuppressive function of ROS. Conclusion: ROS-related signature is an independent prognostic factor in gliomas and could potentially exert immunosuppressive effects on the tumor microenvironment.

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

A novel interplay between PRC2 and miR-3189 regulates epithelial-mesenchymal transition (EMT) via modulating COL6A2 in glioblastoma.

Recent studies have shed light on disrupted collagen signaling in Gliomas, yet the regulatory landscape remains largely unexplored. This study enquired into the role of polycomb repressive complex-2 (PRC2)-mediated H3K27me3 modification, a key epigenetic factor in glioma. Using in-house data, we identified miRNAs downregulated in glioblastoma (GBM) with the potential to regulate Collagen VI family genes. Notably, miR-3189 emerged as a prime PRC2 target. Its expression was significantly downregulated in Indian GBM patients as well as other glioma cohorts. Mechanistic insights, involving Luciferase assays, mutagenesis, and Western blot analysis, confirmed direct targeting of Collagen VI member COL6A2 by miR-3189-3p. Functional assays demonstrated that miR-3189-3p restrained GBM malignancy by inhibiting proliferation, migration, and epithelial-mesenchymal transition (EMT). Conversely, COL6A2 overexpressed in GBM patients, countered miR-3189, and promoted the malignant phenotype. Gene set enrichment analysis highlighted EMT enrichment in GBM patients with elevated COL6A2 expression, carrying prognostic implications. This study uncovers intricate interactions between two epigenetic regulators-H3K27me3 and miR-3189-working synergistically to modulate Collagen VI gene; thus, influencing the malignancy of GBM. Targeting this H3K27me3|miR-3189-3p|COL6A2 axis presents a potential therapeutic avenue against GBM.

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.

PRIM2: A Marker of MYC-driven Hyper-proliferation, Disease Progression, Tumor Aggressiveness and Poor Survival in Glioma Patients.

Gliomas are the most prevalent brain tumors with metabolic alterations playing a pivotal role in disease progression. However, the precise coordination of metabolic alterations with tumor-promoting cellular mechanisms, leading to tumor initiation, progression, and aggressiveness, resulting in poor outcomes, remains poorly understood in gliomas. We conducted a metabolism-targeted differential gene expression analysis using glioma patients' expression profiling data from The Cancer Genome Atlas (TCGA) database. In addition, pathway enrichment analysis, gene set enrichment analysis (GSEA), transcription factor prediction, network construction, and correlation analyses were performed. Survival analyses were performed in R. All results were validated using independent GEO expression datasets. Metabolism-targeted analysis identified 5 hits involved in diverse metabolic processes linking them to disease aggressiveness in gliomas. Subsequently, we established that cell cycle progression and hyper-proliferation are key drivers of tumor progression and aggressiveness in gliomas. One of the identified metabolic hits, DNA primase 2 (PRIM2), a gene involved in DNA replication was found directly associated with cell cycle progression in gliomas. Furthermore, our analysis indicated that PRIM2, along with other cell cycle-related genes, is under the control of and regulated by the oncogenic MYC transcription factor in gliomas. In addition, PRIM2 expression alone is enough to predict MYC-driven cell cycle progression and is associated with tumor progression, aggressive disease state, and poor survival in glioma patients. Our findings highlight PRIM2 as a marker of MYC-driven cell cycle progression and hyper-proliferation, disease onset and progression, tumor aggressiveness, and poor survival in glioma patients.

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.

Analysis of clinical outcome risk factors in glioma

Abstract In this paper, survival curves and Cox regression models were used to form an integrated disease risk factor model. Stepwise Cox regression models using the AIC criterion and the BIC criterion were included in the comparative models, penalties were imposed on the regression parameters for variable selection, and important covariates were selected to analyze censored data so as to analyze the dependence of dichotomous outcome events and survival time on the covariates. Applying the model of this paper to investigate postoperative infection and seizure risk in glioma, the results showed that 104 strains of pathogenic bacteria were detected. Gram-positive bacteria were the most prevalent infection-causing organisms with 67 strains, with Streptococcus grass-green and Staphylococcus epidermidis being the most common. There were 34 strains (32.69%) of gram-negative bacteria, and Acinetobacter baumannii was the most common one. 3 strains (2.88%) of fungi were present. Cox regression analysis was used to screen for five independent risk factors for surgical site infections in patients undergoing glioma surgery: neutrophil ratio, lymphocyte ratio, surgical grade (III), duration of antibiotic use, and postoperative day three temperature. The presence or absence of preoperative epilepsy has an impact on the prognosis of glioma patients, with fluctuating seizures being the most common postoperative condition in patients with grade II-III gliomas, which often recur after 12 months of seizure-free epilepsy. To sum up, the findings of this report are highly instructive in determining the prognosis for glioma treatment.

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.

Development and validation of a personalized classifier to predict the prognosis and response to immunotherapy in glioma based on glycolysis and the tumor microenvironment.

Glycolysis is closely associated with cancer progression and treatment outcomes. However, the role of glycolysis in the immune microenvironment, prognosis, and immunotherapy of glioma remains unclear. This study investigated the role of glycolysis on prognosis and its relationship with the tumor microenvironment (TME). Subsequently, we developed and validated the glycolysis-related gene signature (GRS)-TME classifier using multiple independent cohorts. Furthermore, we also examined the prognostic value, somatic alterations, molecular characteristics, and potential benefits of immunotherapy based on GRS-TME classifier. Lastly, the effect of kinesin family member 20A (KIF20A) on the proliferation and migration of glioma cells was evaluated in vitro. Glycolysis was identified as a significant prognostic risk factor in glioma, and closely associated with an immunosuppressive microenvironment characterized by altered distribution of immune cells. Furthermore, a personalized GRS-TME classifier was developed and validated by combining the glycolysis (18 genes) and TME (seven immune cells) scores. Patients in the GRSlow/TMEhigh subgroup exhibited a more favorable prognosis compared to other subgroups. Distinct genomic alterations and signaling pathways were observed among different subgroups, which are closely associated with cell cycle, epithelial-mesenchymal transition, p53 signaling pathway, and interferon-alpha response. Additionally, we found that patients in the GRSlow/TMEhigh subgroup exhibit a higher response rate to immunotherapy, and the GRS-TME classifier can serve as a novel biomarker for predicting immunotherapy outcomes. Finally, high expression of KIF20A is associated with an unfavorable prognosis in glioma, and its knockdown can inhibit the proliferation and migration of glioma cells. Our study developed a GRS-TME classifier for predicting the prognosis and potential benefits of immunotherapy in glioma patients. Additionally, we identified KIF20A as a prognostic and therapeutic biomarker for glioma.

Circ_0008285 Regulates Glioma Progression via the miR-384/HMGB1 Axis.

Recent studies indicate that circular RNAs (circRNAs) have been implicated in the initiation or progression of a wide spectrum of diseases. In the current study, we explored the potential engagement of circ_0008285 in glioma and investigated the downstream regulators. The detection of circ_0008285 level in glioma specimens and cell lines was conducted by quantitative real-time polymerase chain reaction. The chi-squared test was employed to evaluate the relationship between the circ_0008285 level and the clinical features of glioma patients. The roles of circ_0008285 on the proliferation and apoptosis of glioma cells were studied by knockdown experiment. Meanwhile, the regulatory relationship of circ_0008285, miR-384, and high mobility group protein B1 (HMGB1) was explored in glioma cells, and we explored the effects of circ_0008285/miR-384/HMGB1 pathway on glioma cells. In glioma specimens and cell lines, the expression of circ_0008285 was significantly increased, and a high circ_0008285 level was associated with a larger tumor size and more advanced grading in glioma patients. Furthermore, downregulating circ_0008285 suppressed proliferation and triggered apoptosis of glioma cells, which was associated with a cell cycle arrest at the G1/G0 phase. Mechanism studies indicated that circ_0008285 regulated HMGB1 by sponging miR-384. Functional experiments demonstrated that circ_0008285 promoted the malignant phenotype of glioma cells by miR-384/HMGB1 axis. Our study revealed circ_0008285 as a novel oncogenic factor in glioma through modulating the miR-384/HMGB1 pathway, suggesting that targeting circ_0008285 could serve as a strategy for glioma management.

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.

The PODNL1/AKT/β-catenin signaling axis mediates glioma progression and sensitivity to temozolomide

Abnormal expression of small leucine-rich repeat proteins (SLRP) in tumor tissues has been reported as a critical trigger for tumorigenesis and progression. However, the molecular mechanism of PODNL1, a novel member of SLRP family, in glioma remains largely unknown. Therefore, this study aimed to investigate its correlation with clinical factors by glioma cohort and to identify the molecular mechanisms of aberrant PODNL1 gene expression in glioma. Our findings revealed that both PODNL1 mRNA and protein levels were markedly upregulated in glioma tissues, and high PODNL1 mRNA level was significantly associated with poor prognosis of glioma patients. In functional assays, PODNL1 knockdown significantly suppressed the proliferation and invasion abilities of glioma cells, while overexpression of PODNL1 had the opposite effect both in vitro and in vivo. Mechanistically, PODNL1 knockdown suppressed the activation of AKT/mTOR signaling and inhibited nuclear translocation of β-catenin protein in the glioma cells. Our results suggest that PODNL1 acts as an oncogenic factor in glioma by promoting glioma progression through the activation of the kinase AKT, which indeces β-catenin nuclear translocation. Additionally, PODNL1 knockdown enhanced the sensitivity of glioma cells to temozolomide, a chemotherapeutic agent commonly used in the treatment of glioma. The PODNL1/AKT/β-catenin signaling axis represents a new potential therapeutic target against glioma. Furthermore, our data showed the combination of temozolomide and MK-2206, an AKT inhibitor, had a synergistic antitumor effect against glioma cells.

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.

Revisiting prognostic factors in glioma with leptomeningeal metastases: a comprehensive analysis of clinical and molecular factors and treatment modalities

PurposeTo comprehensively investigate prognostic factors, including clinical and molecular factors and treatment modalities, in adult glioma patients with leptomeningeal metastases (LM).MethodsTotal 226 patients with LM (from 2001 to 2021 among 1495 grade 2 to 4 glioma patients, 88.5% of LM patients being IDH-wildtype) with complete information on IDH mutation, 1p/19q codeletion, and MGMT promoter methylation status were enrolled. Predictors of overall survival (OS) of entire patients were determined by time-dependent Cox analysis, including clinical, molecular, and treatment data. Subgroup analyses were performed for patients with LM at initial diagnosis and LM diagnosed at recurrence (herein, initial and recurrent LM). Identical analyses were performed in IDH-wildtype glioblastoma patients.ResultsMedian OS was 17.0 (IQR 9.7–67.1) months, with shorter median OS in initial LM than recurrent LM patients (12.2 vs 20.6 months, P < 0.001). In entire patients, chemotherapy and antiangiogenic therapy were predictors of longer OS, while male sex and initial LM were predictors of shorter OS. In initial LM, higher KPS, chemotherapy, and antiangiogenic therapy were predictors of longer OS, while male sex was a predictor of shorter OS. In recurrent LM, chemotherapy and longer interval between initial glioma and LM diagnoses were predictors of longer OS, while male sex was a predictor of shorter OS. A similar trend was observed in IDH-wildtype glioblastoma.ConclusionActive chemotherapy and antiangiogenic therapy demonstrated survival benefit in glioma patients with LM. There is consistent female survival advantage, whereas longer interval between initial glioma diagnosis and LM development suggests longer OS in recurrent LM.

LncRNA WEE2-AS1 is a diagnostic biomarker that predicts poor prognoses in patients with glioma

BackgroundGlioma is characterized by high morbidity, high mortality, and poor prognosis. Despite tremendous advances in the treatment of glioma, the prognosis of patients with glioma is still unsatisfactory. There is an urgent need to discover novel molecular markers that effectively predict prognosis in patients with glioma. The investigation of the role of WEE2-AS1 in various tumors is an emerging research field, but the biological function and prognostic value of WEE2-AS1 in glioma have rarely been reported. This study aimed to assess the value of WEE2-AS1 as a potential prognostic marker of glioma.MethodsGene expression (RNA-Seq) data of patients with glioma were extracted from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. The Wilcoxon rank sum test was used to analyze the expression of WEE2-AS1 in the cells and tissues of glioma. The Kruskal–Wallis rank sum test, Wilcoxon rank sum test, and logistic regression were used to evaluate the relationship between clinical variables and expression of WEE2-AS1. Cox regression analysis and the Kaplan–Meier method were used to evaluate the prognostic factors in glioma. A nomogram based on Cox multivariate analysis was used to predict the impact of WEE2-AS1 on glioma prognosis. Gene Set Enrichment Analysis (GSEA) was used to identify key WEE2-AS1-associated signaling pathways. Spearman’s rank correlation was used to elucidate the association between WEE2-AS1 expression and immune cell infiltration levels.ResultsWe found that WEE2-AS1 was overexpressed in a variety of cancers, including glioma. High expression of WEE2-AS1 was associated with glioma progression. We determined that the expression of WEE2-AS1 might be an independent risk factor for the survival and prognosis of patients with glioma. We further observed that the mechanism of WEE2-AS1-mediated tumorigenesis involved neuroactive ligand-receptor interaction, cell cycle, and the infiltration of immune cells into the glioma microenvironment.ConclusionThese findings demonstrate that WEE2-AS1 is a promising biomarker for the diagnosis and prognosis of patients with glioma. An increased understanding of its effects on the regulation of cell growth may lead to the development of clinical applications that improve the prognostic status of patients with glioma.

Reconsidering the role of receptors for SARS‐CoV‐2 in clear cell renal cell carcinoma: Friends or foes

Reconsidering the role of receptors for SARS‐CoV‐2 in clear cell renal cell carcinoma: Friends or foes

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.