Dataset Information

EZH2 is a potential prognostic predictor of glioma.

ABSTRACT: The enhancer of zeste homologue 2 (EZH2) is a histone H3 lysine 27 methyltransferase that promotes tumorigenesis in a variety of human malignancies by altering the expression of tumour suppressor genes. To evaluate the prognostic value of EZH2 in glioma, we analysed gene expression data and corresponding clinicopathological information from the Chinese Glioma Genome Atlas, the Cancer Genome Atlas and GTEx. Increased expression of EZH2 was significantly associated with clinicopathologic characteristics and overall survival as evaluated by univariate and multivariate Cox regression. Gene Set Enrichment Analysis revealed an association of EZH2 expression with the cell cycle, DNA replication, mismatch repair, p53 signalling and pyrimidine metabolism. We constructed a nomogram for prognosis prediction with EZH2, clinicopathologic variables and significantly correlated genes. EZH2 was demonstrated to be significantly associated with several immune checkpoints and tumour-infiltrating lymphocytes. Furthermore, the ESTIMATE and Timer Database scores indicated correlation of EZH2 expression with a more immunosuppressive microenvironment for glioblastoma than for low grade glioma. Overall, our study demonstrates that expression of EZH2 is a potential prognostic molecular marker of poor survival in glioma and identifies signalling pathways and immune checkpoints regulated by EHZ2, suggesting a direction for future application of immune therapy in glioma.

SUBMITTER: Chen YN

PROVIDER: S-EPMC7812280 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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EZH2 is a potential prognostic predictor of glioma.

Chen Yi-Nan YN Hou Shi-Qiang SQ Jiang Rui R Sun Jun-Long JL Cheng Chuan-Dong CD Qian Zhong-Run ZR

Journal of cellular and molecular medicine 20201204 2

The enhancer of zeste homologue 2 (EZH2) is a histone H3 lysine 27 methyltransferase that promotes tumorigenesis in a variety of human malignancies by altering the expression of tumour suppressor genes. To evaluate the prognostic value of EZH2 in glioma, we analysed gene expression data and corresponding clinicopathological information from the Chinese Glioma Genome Atlas, the Cancer Genome Atlas and GTEx. Increased expression of EZH2 was significantly associated with clinicopathologic character ...[more]

PMID: 33277782

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Project description:Glioma is the most common and aggressive tumor type of the central nervous system and is associated with poor prognosis. To date, novel emerging immunotherapies have significantly improved outcomes for patients with various cancer types. Human endogenous retrovirus‑H long terminal repeat‑associating protein 2 (HHLA2), a newly discovered immune checkpoint molecule, has demonstrated its potential as a novel therapeutic target. Therefore, the present study aimed to investigate the clinical prognostic value of HHLA2 in gliomas and its mechanistic role. A systematic review of datasets from The Cancer Genome Atlas was performed. The RNA‑seq data of a total of 669 cases were analyzed and the biological function of HHLA2 was predicted by Gene Ontology (GO) and pathway enrichment analysis. Immunohistochemistry labelling images for HHLA2 was obtained from the Human Protein Atlas. xCell was used to comprehensively analyze the model of tumor‑infiltrating immune cell in glioma. The Cox proportional hazards regression model was used to predict outcomes for glioma patients. The results revealed that the expression levels of HHLA2 were significantly lower in high‑grade glioma, as well as glioma with wild‑type isocitrate dehydrogenase, no deletion of 1p/19q and telomerase reverse transcriptase promoter mutation. Receiver operating characteristic analysis revealed that HHLA2 was a predictor of the neural subtype. The tumor‑infiltrating immune cell model indicated that HHLA2 was negatively associated with tumor‑associated macrophages. GO analysis and pathway enrichment analysis revealed that HHLA2‑associated genes were functionally involved in inhibition of neoplasia‑associated processes. HHLA2 was significantly negatively correlated with certain genes, including interleukin‑10, transforming growth factor‑β, vascular endothelial growth factor and δ‑like canonical Notch ligand 4, and other immune checkpoint molecules, including programmed cell death 1, lymphocyte activating 3 and CD276. Survival analysis indicated that high expression of HHLA2 predicted a favorable prognosis. In conclusion, the present study revealed that upregulation of HHLA2 is significantly associated with a favorable outcome for patients with glioma. Targeting HHLA2 as an immune stimulator may become a valuable approach for the treatment of glioma in clinical practice.

Project description:BackgroundGliomas are the most malignant central nervous system tumors. With the development of sequencing technology, more potential biomarkers related to the treatment, prognosis, and molecular classification of glioma have been identified. Here, we intend to investigate the potential biological function and clinical value of a new biomarker in glioma.MethodsKDELR1 expression data and the corresponding clinical information were downloaded from public databases and then preprocessed using R language. Correlation, Kaplan-Meier survival, and Cox regression analyses were performed to explore the clinical significance of KDELR1 in glioma patients. Furthermore, the immune infiltration and microenvironment parameters were evaluated via TIMER and CIBERSORT. Immunohistochemistry was conducted to confirm the KDELR1 expression and its correlation with immunity infiltration and prognosis.ResultsKDELR1 was upregulated in glioma samples compared with normal brain tissues, and its expression was significantly correlated with age, the World Health Organization (WHO) grade, recurrence, necrosis, microvascular proliferation, molecular classification, isocitrate dehydrogenase (IDH) mutation, and 1p/19q codeletion status. In addition, survival analysis showed that glioma patients with KDELR1 overexpression had shorter overall survival (OS) and disease-free survival times, and Cox regression analysis revealed that KDELR1 acted as an independent prognostic factor of OS in glioma patients. Gene set enrichment analysis indicated a significant enrichment of metabolism-associated pathways. KDELR1 expression was positively associated with immune infiltration (including infiltration by CD8+ T cells, CD4+ T cells, macrophages, and so on) and microenvironment parameters (including stromal, immune, and ESTIMATE scores) in gliomas. The expression of KDELR1 and its correlation with the tumor grade and prognosis were confirmed by immunohistochemistry in clinical samples (n = 119, P < 0.05).ConclusionsTaken together, these findings suggest that KDELR1 is correlated with the tumor grade, molecular classifications, and immune infiltration; highlighting that KDELR1 is a novel and promising biomarker for molecular classification, treatment, and prognostic assessment may further indicate the treating effect of immune therapy.

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EZH2 is a potential prognostic predictor of glioma.

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EZH2 is a potential prognostic predictor of glioma.

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