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TMEFF2 promoter hypermethylation is an unfavorable prognostic marker in gliomas
BACKGROUND: Transmembrane protein with EGF-like and two follistatin-like domains 2 (TMEFF2) is a transmembrane protein in the tomoregulin family. Little research has been performed to determine whether TMEFF2 methylation is a prognostic marker in adult diffuse gliomas. METHODS: In this study, we inv...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931334/ https://www.ncbi.nlm.nih.gov/pubmed/33663520 http://dx.doi.org/10.1186/s12935-021-01818-x |
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author | Xie, Sidi Zhang, Yunxiao Peng, Tao Guo, Jinglin Cao, Yongfu Guo, Jing Shi, Xiaofeng Li, Yaqin Liu, Yawei Qi, Songtao Wang, Hai |
author_facet | Xie, Sidi Zhang, Yunxiao Peng, Tao Guo, Jinglin Cao, Yongfu Guo, Jing Shi, Xiaofeng Li, Yaqin Liu, Yawei Qi, Songtao Wang, Hai |
author_sort | Xie, Sidi |
collection | PubMed |
description | BACKGROUND: Transmembrane protein with EGF-like and two follistatin-like domains 2 (TMEFF2) is a transmembrane protein in the tomoregulin family. Little research has been performed to determine whether TMEFF2 methylation is a prognostic marker in adult diffuse gliomas. METHODS: In this study, we investigated TMEFF2 expression in surgical glioma tissue samples. In addition, we conducted bisulfite amplicon sequencing (BSAS) and methylation-specific PCR (MSP) to evaluate TMEFF2 methylation in glioblastoma (GBM) cells. Subsequently, we investigated the biological function of TMEFF2 in GBM cells. Moreover, we explored the prognostic significance of TMEFF2 in gliomas by analysing a cohort dataset from TCGA. RESULTS: Immunohistochemistry analysis of 75 paired glioma tumour and peritumoural tissues demonstrated that glioma tumour tissues expressed lower TMEFF2 levels than peritumoural tissues (P < 0.001). TMEFF2 promoter methylation levels were increased in glioblastoma cells compared with SVG p12 cells (P < 0.001). Inhibition of methylation reduced TMEFF2 methylation and increased its expression in LN229 and T98G cells (P < 0.05). Knockdown of TMEFF2 expression significantly promoted the proliferation of U87MG cells and primary GBM cells (P < 0.05). TMEFF2 methylation is negatively associated with IDH1, ATRX and TP53 mutations, and the subtype of glioma harbouring combined IDH1/ATRX/TP53 mutations was associated with low TMEFF2 methylation levels. Survival analysis confirmed that low TMEFF2 methylation levels are associated with good prognosis in glioma patients. CONCLUSIONS: Our results suggest that TMEFF2 DNA methylation might be associated with glioma tumour progression and could serve as a valuable prognostic marker for adult diffuse gliomas. |
format | Online Article Text |
id | pubmed-7931334 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-79313342021-03-05 TMEFF2 promoter hypermethylation is an unfavorable prognostic marker in gliomas Xie, Sidi Zhang, Yunxiao Peng, Tao Guo, Jinglin Cao, Yongfu Guo, Jing Shi, Xiaofeng Li, Yaqin Liu, Yawei Qi, Songtao Wang, Hai Cancer Cell Int Primary Research BACKGROUND: Transmembrane protein with EGF-like and two follistatin-like domains 2 (TMEFF2) is a transmembrane protein in the tomoregulin family. Little research has been performed to determine whether TMEFF2 methylation is a prognostic marker in adult diffuse gliomas. METHODS: In this study, we investigated TMEFF2 expression in surgical glioma tissue samples. In addition, we conducted bisulfite amplicon sequencing (BSAS) and methylation-specific PCR (MSP) to evaluate TMEFF2 methylation in glioblastoma (GBM) cells. Subsequently, we investigated the biological function of TMEFF2 in GBM cells. Moreover, we explored the prognostic significance of TMEFF2 in gliomas by analysing a cohort dataset from TCGA. RESULTS: Immunohistochemistry analysis of 75 paired glioma tumour and peritumoural tissues demonstrated that glioma tumour tissues expressed lower TMEFF2 levels than peritumoural tissues (P < 0.001). TMEFF2 promoter methylation levels were increased in glioblastoma cells compared with SVG p12 cells (P < 0.001). Inhibition of methylation reduced TMEFF2 methylation and increased its expression in LN229 and T98G cells (P < 0.05). Knockdown of TMEFF2 expression significantly promoted the proliferation of U87MG cells and primary GBM cells (P < 0.05). TMEFF2 methylation is negatively associated with IDH1, ATRX and TP53 mutations, and the subtype of glioma harbouring combined IDH1/ATRX/TP53 mutations was associated with low TMEFF2 methylation levels. Survival analysis confirmed that low TMEFF2 methylation levels are associated with good prognosis in glioma patients. CONCLUSIONS: Our results suggest that TMEFF2 DNA methylation might be associated with glioma tumour progression and could serve as a valuable prognostic marker for adult diffuse gliomas. BioMed Central 2021-03-04 /pmc/articles/PMC7931334/ /pubmed/33663520 http://dx.doi.org/10.1186/s12935-021-01818-x Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Primary Research Xie, Sidi Zhang, Yunxiao Peng, Tao Guo, Jinglin Cao, Yongfu Guo, Jing Shi, Xiaofeng Li, Yaqin Liu, Yawei Qi, Songtao Wang, Hai TMEFF2 promoter hypermethylation is an unfavorable prognostic marker in gliomas |
title | TMEFF2 promoter hypermethylation is an unfavorable prognostic marker in gliomas |
title_full | TMEFF2 promoter hypermethylation is an unfavorable prognostic marker in gliomas |
title_fullStr | TMEFF2 promoter hypermethylation is an unfavorable prognostic marker in gliomas |
title_full_unstemmed | TMEFF2 promoter hypermethylation is an unfavorable prognostic marker in gliomas |
title_short | TMEFF2 promoter hypermethylation is an unfavorable prognostic marker in gliomas |
title_sort | tmeff2 promoter hypermethylation is an unfavorable prognostic marker in gliomas |
topic | Primary Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931334/ https://www.ncbi.nlm.nih.gov/pubmed/33663520 http://dx.doi.org/10.1186/s12935-021-01818-x |
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