Enhancer of zeste homolog 2 is a negative prognostic biomarker and correlated with immune infiltrates in meningioma

BackgroundEnhancer of zeste homolog 2 (EZH2), an important epigenetic regulator, that mainly regulates histone H3 lysine 27 trimethylation (H3K27me3) through histone methyltransferase, and participates in promoting the development of tumors. At present, the loss of H3K27me3 expression in meningioma...

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Main Authors: Jing Zeng, Lu Sun, Jiaming Huang, Xia Yang, Wanming Hu
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-11-01
Series:Frontiers in Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fnins.2022.1076530/full
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author Jing Zeng
Jing Zeng
Lu Sun
Lu Sun
Jiaming Huang
Jiaming Huang
Xia Yang
Xia Yang
Wanming Hu
Wanming Hu
author_facet Jing Zeng
Jing Zeng
Lu Sun
Lu Sun
Jiaming Huang
Jiaming Huang
Xia Yang
Xia Yang
Wanming Hu
Wanming Hu
author_sort Jing Zeng
collection DOAJ
description BackgroundEnhancer of zeste homolog 2 (EZH2), an important epigenetic regulator, that mainly regulates histone H3 lysine 27 trimethylation (H3K27me3) through histone methyltransferase, and participates in promoting the development of tumors. At present, the loss of H3K27me3 expression in meningioma is a poor prognostic factor, but the research of EZH2 in meningioma is rare. Therefore, we aim to explore the expression of EZH2 in the meningioma and its correlation with the prognosis and immune microenvironment and lay the foundation for the subsequently potential targeted therapy and immunotherapy for meningioma.MethodsTissue microarray immunohistochemistry staining was performed on 276 meningioma samples from Sun Yat-sen University Cancer Center. Expression levels of EZH2, H3K27me3, Ki67, programmed cell death protein 1 (PD-1), programmed cell death 1 ligand 1 (PD-L1), CD4, CD8, CD20, FOXP3, CD68, and CD163 were evaluated. Cox regression analyses were performed, and the Kaplan–Meier (KM) method was used to construct survival curves. In addition, we use biological information methods to analyze the mRNA expression of EZH2 and its relationship with the prognosis and immune microenvironment in the gene expression omnibus (GEO) database.ResultsEnhancer of zeste homolog 2 expression is concentrated in World Health Organization (WHO) grades 2 and 3 meningiomas (8.3+ and 33.3%+). We found that EZH2 expression was associated with a worse prognosis in meningioma (P < 0.001), the same results were confirmed in the GEO database (P < 0.001). Both EZH2 expression and H3K27me3 deletion (P = 0.035) predicted a worse prognosis, but EZH2 has no correlation with H3K27me3 expression. EZH2 expression was closely associated with increased Ki67 index (P < 0.001). In addition, EZH2 was associated with the immune microenvironment and positively correlated with PD-L1 expression (P < 0.001).ConclusionEnhancer of zeste homolog 2 is a new prognostic biomarker in meningioma. It correlates with PD-L1 expression and closely related to tumor immunosuppression. Our research can provide a reference for the potential targeted therapy and immunotherapy of meningioma in the future.
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spelling doaj.art-13f2331a6fa44186a666041d6e6c85d72022-12-22T04:36:40ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2022-11-011610.3389/fnins.2022.10765301076530Enhancer of zeste homolog 2 is a negative prognostic biomarker and correlated with immune infiltrates in meningiomaJing Zeng0Jing Zeng1Lu Sun2Lu Sun3Jiaming Huang4Jiaming Huang5Xia Yang6Xia Yang7Wanming Hu8Wanming Hu9Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaState Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Guangzhou, ChinaDepartment of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaState Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Guangzhou, ChinaDepartment of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaState Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Guangzhou, ChinaDepartment of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaState Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Guangzhou, ChinaDepartment of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaState Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Guangzhou, ChinaBackgroundEnhancer of zeste homolog 2 (EZH2), an important epigenetic regulator, that mainly regulates histone H3 lysine 27 trimethylation (H3K27me3) through histone methyltransferase, and participates in promoting the development of tumors. At present, the loss of H3K27me3 expression in meningioma is a poor prognostic factor, but the research of EZH2 in meningioma is rare. Therefore, we aim to explore the expression of EZH2 in the meningioma and its correlation with the prognosis and immune microenvironment and lay the foundation for the subsequently potential targeted therapy and immunotherapy for meningioma.MethodsTissue microarray immunohistochemistry staining was performed on 276 meningioma samples from Sun Yat-sen University Cancer Center. Expression levels of EZH2, H3K27me3, Ki67, programmed cell death protein 1 (PD-1), programmed cell death 1 ligand 1 (PD-L1), CD4, CD8, CD20, FOXP3, CD68, and CD163 were evaluated. Cox regression analyses were performed, and the Kaplan–Meier (KM) method was used to construct survival curves. In addition, we use biological information methods to analyze the mRNA expression of EZH2 and its relationship with the prognosis and immune microenvironment in the gene expression omnibus (GEO) database.ResultsEnhancer of zeste homolog 2 expression is concentrated in World Health Organization (WHO) grades 2 and 3 meningiomas (8.3+ and 33.3%+). We found that EZH2 expression was associated with a worse prognosis in meningioma (P < 0.001), the same results were confirmed in the GEO database (P < 0.001). Both EZH2 expression and H3K27me3 deletion (P = 0.035) predicted a worse prognosis, but EZH2 has no correlation with H3K27me3 expression. EZH2 expression was closely associated with increased Ki67 index (P < 0.001). In addition, EZH2 was associated with the immune microenvironment and positively correlated with PD-L1 expression (P < 0.001).ConclusionEnhancer of zeste homolog 2 is a new prognostic biomarker in meningioma. It correlates with PD-L1 expression and closely related to tumor immunosuppression. Our research can provide a reference for the potential targeted therapy and immunotherapy of meningioma in the future.https://www.frontiersin.org/articles/10.3389/fnins.2022.1076530/fullEZH2meningiomaH3K27me3GEOPD-L1immune infiltrates
spellingShingle Jing Zeng
Jing Zeng
Lu Sun
Lu Sun
Jiaming Huang
Jiaming Huang
Xia Yang
Xia Yang
Wanming Hu
Wanming Hu
Enhancer of zeste homolog 2 is a negative prognostic biomarker and correlated with immune infiltrates in meningioma
Frontiers in Neuroscience
EZH2
meningioma
H3K27me3
GEO
PD-L1
immune infiltrates
title Enhancer of zeste homolog 2 is a negative prognostic biomarker and correlated with immune infiltrates in meningioma
title_full Enhancer of zeste homolog 2 is a negative prognostic biomarker and correlated with immune infiltrates in meningioma
title_fullStr Enhancer of zeste homolog 2 is a negative prognostic biomarker and correlated with immune infiltrates in meningioma
title_full_unstemmed Enhancer of zeste homolog 2 is a negative prognostic biomarker and correlated with immune infiltrates in meningioma
title_short Enhancer of zeste homolog 2 is a negative prognostic biomarker and correlated with immune infiltrates in meningioma
title_sort enhancer of zeste homolog 2 is a negative prognostic biomarker and correlated with immune infiltrates in meningioma
topic EZH2
meningioma
H3K27me3
GEO
PD-L1
immune infiltrates
url https://www.frontiersin.org/articles/10.3389/fnins.2022.1076530/full
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