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Nonglioblastomatous diffuse glioma (non-GDG) is a heterogeneous neuroepithelial tumor that exhibits a varied survival range from 4 to 13 years based on the diverse subtypes. Recent studies demonstrated novel molecular markers can predict prognosis for non-GDG patients; however, these findings as well as pathological classification strategies show obvious limitations on malignant transition due to the heterogeneity among non-GDGs. Therefore, developing reliable prognostic biomarkers and therapeutic targets have become an urgent need for precisely distinguishing non-GDG subtypes, illuminating the underlying mechanism. Nuclear factor κβ (NF-κB) has been proved to be a significant nuclear transcriptional regulator with specific DNA-binding sequences to participate in multiple pathophysiological processes. However, the underlying mechanism of NF-κB activation still needs to be further investigated. Herein, our results indicated retinol-binding protein 1 (RBP1) was significantly upregulated in the IDH WT and 1p19q Non co-del non-GDG subtypes and enriched RBP1 expression was markedly correlated with more severe outcomes. Additionally, malignant signatures of the non-GDG cells including proliferation, migration, invasion, and self-renewal were significantly suppressed by lentiviral knockdown of RBP1. To further explore the underlying molecular mechanism, bioinformatics analysis was performed using databases, and the results demonstrated RBP1 was strongly correlated with tumor necrosis factor α (TNFα)-NF-κB signaling. Moreover, exogenous silencing of RBP1 reduced phosphorylation of IkB-kinase α (IKKα) and thus decreased NF-κB expression via decreasing the degradation of the IκBα protein. Altogether, these data suggested RBP1-dependent activation of NF-κB signaling promoted malignancy of non-GDG, indicating that RBP1 could be a reliable prognostic biomarker and potential therapeutic target for non-GDG., (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Objectives: Studies have demonstrated that genetic variants in the miRNA-coding genes might be associated with cancer susceptibility and survival. Here, we aimed to investigate the influence of MIR3142HG single-nucleotide polymorphisms on the individual's susceptibility to and patients' prognosis of glioma., Materials and Methods: Six variants were genotyped by Agena MassARRAY iPLEX Gold assay among 529 glioma patients and 502 healthy controls. Association of MIR3142HG polymorphisms with the risk for and prognosis of glioma was analyzed by logistic regression analysis and Cox proportional hazards model, respectively., Results: In the risk analysis, rs17057846 (odds ratio [OR]=1.93, P=0.047), rs2961920 (OR=1.53, P=0.019), and rs58747524 (OR=1.23, P=0.046) polymorphisms were associated with increased glioma risk, while rs7727115 (OR=0.76, P=0.030) and rs1582417 (female individuals, OR=0.49, P=0.017) variants were associated with decreased risk. In the survival analysis, rs1582417 polymorphism (hazard ratio=1.26, P=0.017) contributed to poorer prognosis overall. Rs17057846, rs1582417, and rs2431689 polymorphisms were associated with prognosis of astrocytoma, and rs1582417, rs17057846, and rs58747524 variants were associated with the survival rate in patients with low-grade glioma (I to II)., Conclusion: Our study provided the first evidence for the impact of rs1582417, rs17057846, rs2431689, rs2961920, rs58747524, and rs7727115 polymorphisms in MIR3142HG on the susceptibility to and/or prognosis of glioma in the Chinese Han population.

Background: Abnormal expression of the mastermind-like transcriptional co-activator 2 (MAML2) gene is oncogenic in several human cancers, including glioma. However, the relevance of MAML2 variants with glioma remains unknown. We aimed to investigate the role of MAML2 polymorphisms in glioma risk and prognosis among the Chinese Han population., Methods: Seven MAML2 single-nucleotide polymorphisms (SNPs) were genotyped using Agena MassARRAY system among 575 patients with glioma and 500 age- and gender-matched healthy controls. Logistic regression was used to estimate the association between MAML2 polymorphisms and glioma risk by calculating odds ratios (ORs) and 95% confidence intervals (CI). Kaplan-Meier survival analysis and univariate, multivariate Cox proportional hazard regression analyses for hazard ratios (HRs) and 95% CIs were performed to evaluate the contribution of MAML2 polymorphisms to glioma prognosis., Results: MAML2 rs7938889 and rs485842 polymorphisms were associated with the reduced risk of glioma (OR = 0.69, P=0.023; and OR = 0.81, P=0.032, respectively). Rs7115578 polymorphism had a lower susceptibility to glioma in males (OR = 0.68, P=0.034), while rs4598633 variant with a higher risk in females (OR = 1.66, P=0.016). Additionally, rs7115578 AG genotype represented a poorer prognosis of glioma (HR = 1.24, P=0.033) and astrocytoma (log-rank P=0.037, HR = 1.31, P=0.036). Furthermore, rs11021499 polymorphism had lower overall survival (OS) and progression-free survival (PFS) in patients with low-grade glioma., Conclusion: We provided some novel data suggesting MAML2 polymorphisms might contribute to glioma risk and prognosis. Future studies are warranted to validate these findings and characterize mechanisms underlying these associations., (© 2019 The Author(s).)

Objectives: Aurora kinase B (AURKB) and Ubiquitin conjugating enzyme E2C (UBE2C) are involved in tumorigenesis of gliomas and other malignancies as well, but their clinicopathologic significance in gliomas is unknown and the prognostic value of combined expression of AURKB and UBE2C has not been explored. In this study, we investigate the correlation between glioma prognosis and combined expressions of AURKB and UBE2C thus to identify novel therapeutic targets and prognostic biomarkers for glioma patients., Methods: AURKB was identified as one of the key candidate kinase-encoding genes in three different databases by using kinome-wide bioinformatic analysis. Afterwards, UBE2C was chosen as the most closely relevant genes to AURKB according to Spearman correlation test. Then the expressions of AURKB and UBE2C at either transcriptome or protein levels were measured by quantitative Real-time PCR (qRT-PCR) or immunohistochemistry (IHC), respectively. Additionally, Kaplan-Meier analyses were conducted using data from TCGA, Rembrandt and our clinical center to investigate the clinical significance of AURKB and UBE2C. Furthermore, receiver operating characteristic (ROC) analysis was performed to evaluate the sensitivity and specificity of AURKB and UBE2C in predicting the outcomes of glioma patients. Moreover, survival data of patients who underwent post-surgical chemo/radio treatment were extracted and the Kaplan-Meier analyses were performed to investigate the correlation between treatment resistance and combined expressions of AURKB and UBE2C., Results: Both AURKB and UBE2C were significantly up-regulated in gliomas compared to normal brain tissues and the combined elevation of AURKB and UBE2C were strongly associated with histological classification in glioma. Moreover, overexpression of either AURKB or UBE2C strongly correlated to more severe overall survival. Notably, upregulation of these two genes revealed unfavorable outcomes (shorter overall survival and therapy resistance) in glioma patients with significant sensitivity and specificity., Conclusion: Simultaneously elevated expressions of AURKB and UBE2C was strongly correlated to poor prognosis and therapy resistance in glioma, furthermore, our data suggest for the first time that the combination of AURKB and UBE2C overexpression could be highly sensitive prognostic markers and potential therapeutic targets for glioma patients., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Background: Glioma, the most common primary malignant brain tumor, is highly malignant with a poor prognosis. We aimed to clarify the relevance of ANXA5 polymorphisms to glioma risk and prognosis among the Chinese Han population., Method: Six single-nucleotide polymorphisms (SNPs) of ANXA5 were genotyped by Agena MassARRAY in 593 glioma patients and 589 healthy controls. Logistic regression model was used to calculate odds ratios (OR) and 95% confidence intervals (CI). The association between polymorphisms and survival were evaluated using the log-rank test, Kaplan-Meier analysis and Cox regression model., Results: We found that rs117677079 polymorphism was strongly associated with an increased risk of glioma (OR 1.64, p = 0.003) and a worse prognosis for glioma, especially in high-grade glioma (HR 1.76, p = 0.005). Whereas, rs145619195 CT genotype might weaken the susceptibility (OR 0.63, p = 0.024) and prognosis (HR 0.20, p = 0.025) of glioma. Haplotype analysis showed that haplotype ″GACCG″ in the block (rs41278075, rs2306420, rs117677079, rs2306415 and rs1131239) significantly decreased the susceptibility of glioma (OR 0.61, p = 0.003). Furthermore, we also found that age, extent of resection and chemotherapy were key prognostic factors in glioma patients., Conclusion: This study firstly provided evidence for the impact of ANXA5 polymorphism on the susceptibility and prognosis of glioma, suggesting ANXA5 variants might have potential roles in the etiology of glioma.

Interleukin-10 (IL-10) and DNA repair gene PRKDC mutations are implicated in the development of multiple human cancers, including glioma. We investigated associations between IL-10 and PRKDC gene polymorphisms and prognosis in low- and high-grade glioma patients. We analyzed the associations of one IL-10 and one PRKDC single nucleotide polymorphism with patient clinical factors in 481 glioma patients using Cox proportional hazard models and Kaplan-Meier curves. We also assessed associations between patient clinical characteristics and prognosis. Our data showed that the extent of tumor resection (gross-total resection) and application of chemotherapy were associated with improved patient outcomes in all glioma cases. Additionally, univariate (Log-rank p = 0.019) and multivariate Cox regression analyses (p = 0.022) showed that the IL-10 rs1800871 C/T genotype correlates with improved overall survival in cases of low-grade glioma, whereas the PRKDC rs7003908 C/C genotype correlated with reduced overall and progression-free survival in high-grade glioma patients in univariate (Log-rank p = 0.000 and p = 0.000, respectively) and multivariate Cox regression analyses (p = 0.001; p = 0.002, respectively). These results suggest that IL-10 rs1800871 and PRKDC rs7003908 may be useful biomarkers for predicting glioma patient outcome. Further functional studies are needed to evaluate the mechanisms by which these polymorphisms affect glioma progression.