Effects of 1p/19q Codeletion on Immune Phenotype in Low Grade Glioma

Lv, Lei; Zhang, Yuliu; Zhao, Yujia; Wei, Qinqin; Zhao, Ye; Yi, Qiyi

doi:10.3389/fncel.2021.704344

Cited by 25 publications

(16 citation statements)

References 69 publications

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“…LGGs with the 1p/19q codeletion exhibited less immune cell in ltration and lower immune checkpoint gene expression than LGGs with the 1p/19q non-codeletion [50]. This study partly ascribed this interesting phenomenon to the copy number deletion of more than 40 genes encoding cytokines/chemokines that are located on chromosome 1p/19q.…”

Section: Discussionmentioning

confidence: 83%

TEAD4 Serves as a Prognostic Biomarker and Correlates With Immune Phenotype in Lower-Grade Gliomas

Huang

Zhu

et al. 2021

Preprint

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Background: Tumor-infiltrating immune cells (TIICs), which play a pivotal role in the tumor microenvironment, are intimately related to tumor progression and clinical outcome. It remains unclear which factors influence tumor immune infiltration in lower-grade gliomas (LGGs). TEAD4 (TEA Domain Transcription Factor 4) is an essential member of the Hippo pathway that is involved in cancer progression, epithelial-mesenchymal transition, metastasis, and cancer stem cell function across multiple types of cancers. However, the prognostic value of TEAD4 and its association with TIICs in LGG have been hardly studied. Methods: LGG data were obtained from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA). TEAD4 expression between different groups was compared by R and survival analysis was implemented by Kaplan–Meier curves. In Virto experiments were conducted to investigate the role of TEAD4 in glioma cells. Gene set enrichment analysis (GSEA) and protein-protein interaction (PPI) network were used to investigate the differential biological processes and signaling pathways. Multiple computational methods were employed to estimate the association between TEAD4 expression and tumor microenvironment in LGG. Correlations were analyzed by Spearman correlationResults: TEAD4 expression was up-regulated in higher-grade gliomas and correlated with a poorer clinical outcome. Glioma cell proliferation and migration were promoted by TEAD4 overexpression. GSEA and PPI network indicated that multiple immune-related pathways and hub genes were closely associated with TEAD4 expression in LGG specimens. TEAD4 expression was negatively associated with glioma purity. Multivariate Cox regression analysis indicated that TEAD4 expression and tumor purity were independent prognostic factors in LGG. TEAD4 expression was positively correlated with the infiltration of multiple immune cells, including plasma cells, CD8+ T cells, and macrophages M1 and M2. Correlation analysis showed that the TEAD4 level can predict the efficacy of immune checkpoint blockade therapy. Conclusions: TEAD4 is highly related to glioma malignancy grades and multiple immune cell infiltration, suggesting TEAD4 can serve as a new biomarker for anti-cancer therapies in LGG.

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Section: Discussionmentioning

confidence: 83%

TEAD4 Serves as a Prognostic Biomarker and Correlates With Immune Phenotype in Lower-Grade Gliomas

Huang

Zhu

et al. 2021

Preprint

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“…According to the tumor grades, in TCGA database, compared with WHO II and III, the transcription levels of MS4A4A, MS4A4E, MS4A6A, MS4A7, TMEM176A, and TMEM176B were the highest in WHO IV ( Figure 2A ). IDH1/2 mutation and chromosome 1p/19q codel represent driver events during glioma tumorigenesis and are associated with better survival rates in glioma ( Lv et al, 2021 ). Therefore, we studied the expression level of MS4As in the IDH mutant and wild type.…”

Section: Resultsmentioning

confidence: 99%

Comprehensive Analysis of Expression and Prognostic Value of MS4As in Glioma

et al. 2022

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Glioma is the most common malignancy of the nervous system with high mortality rates. The MS4A family members have been reported as potential prognostic biomarkers in several cancers; however, the relationship between the MS4A family and glioma has not been clearly confirmed. In our study, we explored the prognostic value of MS4As as well as their potential pro-cancer mechanisms of glioma. Using bioinformatics analysis methods based on the data from public databases, we found that the expression of MS4A4A, MS4A4E, MS4A6A, MS4A7, TMEM176A, and TMEM176B was significantly overexpressed in glioma tissues compared with that of normal tissues. The Kaplan–Meier method and Cox proportional hazards models revealed that high levels of MS4As can be associated with a poorer prognosis; TMEM176A, TMEM176B, age, WHO grade, and IDH status were identified as independent prognostic factors. Enrichment analysis predicted that MS4As were related to tumor-related pathways and immune response, which might regulate the process of MS4As promoting tumorigenesis. Additionally, we analyzed the correlations of MS4A expression with immune cells and immune inhibitory molecules. Finally, data from the cell culture suggested that knockdown of the TMEM176B gene contributes to the decreased proliferation and migration of glioma cells. In conclusion, MS4A4A, MS4A4E, MS4A6A, MS4A7, TMEM176A, and TMEM176B may act as potential diagnostic or prognostic biomarkers in glioma and play a role in forming the immune microenvironment in gliomas.

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“…1p19q codeletion and MGMTp methylation have been confirmed to be beneficial to survival and markers for patients with high sensitivity to adjuvant chemotherapy in guiding the post-surgery treatment (Morris and Lassman, 2010;Omuro and DeAngelis, 2013). Furthermore, a recent study confirms that 1p19q codeleted WHO II and III gliomas are accompanied with decreased levels of immune infiltrates and epigenetic silencing of immune checkpoints, compared with the 1p19q non-codeletion counterparts, leading to the unsuitable immunotherapy for 1p19q codeleted LGGs (Lv et al, 2021). IDH mutation is an early event in the formation of several diffuse gliomas, which is considered to be the strongest prognostic factor for glioma (Han et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Tumor Immune Microenvironment Landscape in Glioma Identifies a Prognostic and Immunotherapeutic Signature

Zhang

Guo

et al. 2021

Front. Cell Dev. Biol.

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The tumor immune microenvironment (TIME) has been recognized to be associated with sensitivity to immunotherapy and patient prognosis. Recent research demonstrates that assessing the TIME patterns on large-scale samples will expand insights into TIME and will provide guidance to formulate immunotherapy strategies for tumors. However, until now, thorough research has not yet been reported on the immune infiltration landscape of glioma. Herein, the CIBERSORT algorithm was used to unveil the TIME landscape of 1,975 glioma observations. Three TIME subtypes were established, and the TIMEscore was calculated by least absolute shrinkage and selection operator (LASSO)–Cox analysis. The high TIMEscore was distinguished by an elevated tumor mutation burden (TMB) and activation of immune-related biological process, such as IL6-JAK-STAT3 signaling and interferon gamma (IFN-γ) response, which may demonstrate that the patients with high TIMEscore were more sensitive to immunotherapy. Multivariate analysis revealed that the TIMEscore could strongly and independently predict the prognosis of gliomas [Chinese Glioma Genome Atlas (CGGA) cohort: hazard ratio (HR): 2.134, p < 0.001; Gravendeel cohort: HR: 1.872, p < 0.001; Kamoun cohort: HR: 1.705, p < 0.001; The Cancer Genome Atlas (TCGA) cohort: HR: 2.033, p < 0.001; the combined cohort: HR: 1.626, p < 0.001], and survival advantage was evident among those who received chemotherapy. Finally, we validated the performance of the signature in human tissues from Wuhan University (WHU) dataset (HR: 15.090, p = 0.008). Our research suggested that the TIMEscore could be applied as an effective predictor for adjuvant therapy and prognosis assessment.

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Effects of 1p/19q Codeletion on Immune Phenotype in Low Grade Glioma

Cited by 25 publications

References 69 publications

TEAD4 Serves as a Prognostic Biomarker and Correlates With Immune Phenotype in Lower-Grade Gliomas

TEAD4 Serves as a Prognostic Biomarker and Correlates With Immune Phenotype in Lower-Grade Gliomas

Comprehensive Analysis of Expression and Prognostic Value of MS4As in Glioma

Tumor Immune Microenvironment Landscape in Glioma Identifies a Prognostic and Immunotherapeutic Signature

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