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MR1 overexpression correlates with poor clinical prognosis in glioma patients

BACKGROUND: Glioblastoma is the most common adult primary brain tumor with near-universal fatality. Major histocompatibility complex (MHC) class I molecules are important mediators of CD8 activation and can be downregulated by cancer cells to escape immune surveillance. MR1 is a nonclassical MHC-I-l...

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Autores principales: Kubica, Phillip, Lara-Velazquez, Montserrat, Bam, Marpe, Siraj, Seema, Ong, Irene, Liu, Peng, Priya, Raj, Salamat, Shahriar, Brutkiewicz, Randy R, Dey, Mahua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080245/
https://www.ncbi.nlm.nih.gov/pubmed/33948562
http://dx.doi.org/10.1093/noajnl/vdab034
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author Kubica, Phillip
Lara-Velazquez, Montserrat
Bam, Marpe
Siraj, Seema
Ong, Irene
Liu, Peng
Priya, Raj
Salamat, Shahriar
Brutkiewicz, Randy R
Dey, Mahua
author_facet Kubica, Phillip
Lara-Velazquez, Montserrat
Bam, Marpe
Siraj, Seema
Ong, Irene
Liu, Peng
Priya, Raj
Salamat, Shahriar
Brutkiewicz, Randy R
Dey, Mahua
author_sort Kubica, Phillip
collection PubMed
description BACKGROUND: Glioblastoma is the most common adult primary brain tumor with near-universal fatality. Major histocompatibility complex (MHC) class I molecules are important mediators of CD8 activation and can be downregulated by cancer cells to escape immune surveillance. MR1 is a nonclassical MHC-I-like molecule responsible for the activation of a subset of T cells. Although high levels of MR1 expression should enhance cancer cell recognition, various tumors demonstrate MR1 overexpression with unknown implications. Here, we study the role of MR1 in glioma. METHODS: Using multi-omics data from the Cancer Genome Atlas (TCGA), we studied MR1 expression patterns and its impact on survival for various solid tumors. In glioma specifically, we validated MR1 expression by histology, elucidate transcriptomic profiles of MR1 high versus low gliomas. To understand MR1 expression, we analyzed the methylation status of the MR1 gene and MR1 gene-related transcription factor (TF) expression. RESULTS: MR1 is overexpressed in all grades of glioma and many other solid cancers. However, only in glioma, MR1 overexpression correlated with poor overall survival and demonstrated global dysregulation of many immune-related genes in an MR1-dependent manner. MR1 overexpression correlated with decreased MR1 gene methylation and upregulation of predicted MR1 promoter binding TFs, implying MR1 gene methylation might regulate MR1 expression in glioma. CONCLUSIONS: Our in silico analysis shows that MR1 expression is a predictor of clinical outcome in glioma patients and is potentially regulated at the epigenetic level, resulting in immune-related genes dysregulation. These findings need to be validated using independent in vitro and in vivo functional studies.
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spelling pubmed-80802452021-05-03 MR1 overexpression correlates with poor clinical prognosis in glioma patients Kubica, Phillip Lara-Velazquez, Montserrat Bam, Marpe Siraj, Seema Ong, Irene Liu, Peng Priya, Raj Salamat, Shahriar Brutkiewicz, Randy R Dey, Mahua Neurooncol Adv Basic and Translational Investigations BACKGROUND: Glioblastoma is the most common adult primary brain tumor with near-universal fatality. Major histocompatibility complex (MHC) class I molecules are important mediators of CD8 activation and can be downregulated by cancer cells to escape immune surveillance. MR1 is a nonclassical MHC-I-like molecule responsible for the activation of a subset of T cells. Although high levels of MR1 expression should enhance cancer cell recognition, various tumors demonstrate MR1 overexpression with unknown implications. Here, we study the role of MR1 in glioma. METHODS: Using multi-omics data from the Cancer Genome Atlas (TCGA), we studied MR1 expression patterns and its impact on survival for various solid tumors. In glioma specifically, we validated MR1 expression by histology, elucidate transcriptomic profiles of MR1 high versus low gliomas. To understand MR1 expression, we analyzed the methylation status of the MR1 gene and MR1 gene-related transcription factor (TF) expression. RESULTS: MR1 is overexpressed in all grades of glioma and many other solid cancers. However, only in glioma, MR1 overexpression correlated with poor overall survival and demonstrated global dysregulation of many immune-related genes in an MR1-dependent manner. MR1 overexpression correlated with decreased MR1 gene methylation and upregulation of predicted MR1 promoter binding TFs, implying MR1 gene methylation might regulate MR1 expression in glioma. CONCLUSIONS: Our in silico analysis shows that MR1 expression is a predictor of clinical outcome in glioma patients and is potentially regulated at the epigenetic level, resulting in immune-related genes dysregulation. These findings need to be validated using independent in vitro and in vivo functional studies. Oxford University Press 2021-02-20 /pmc/articles/PMC8080245/ /pubmed/33948562 http://dx.doi.org/10.1093/noajnl/vdab034 Text en © The Author(s) 2021. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Basic and Translational Investigations
Kubica, Phillip
Lara-Velazquez, Montserrat
Bam, Marpe
Siraj, Seema
Ong, Irene
Liu, Peng
Priya, Raj
Salamat, Shahriar
Brutkiewicz, Randy R
Dey, Mahua
MR1 overexpression correlates with poor clinical prognosis in glioma patients
title MR1 overexpression correlates with poor clinical prognosis in glioma patients
title_full MR1 overexpression correlates with poor clinical prognosis in glioma patients
title_fullStr MR1 overexpression correlates with poor clinical prognosis in glioma patients
title_full_unstemmed MR1 overexpression correlates with poor clinical prognosis in glioma patients
title_short MR1 overexpression correlates with poor clinical prognosis in glioma patients
title_sort mr1 overexpression correlates with poor clinical prognosis in glioma patients
topic Basic and Translational Investigations
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080245/
https://www.ncbi.nlm.nih.gov/pubmed/33948562
http://dx.doi.org/10.1093/noajnl/vdab034
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