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MN1 overexpression with varying tumor grade is a promising predictor of survival of glioma patients

Gliomas have substantial mortality to incidence rate ratio and a dismal clinical course. Newer molecular insights, therefore, are imperative to refine glioma diagnosis, prognosis and therapy. Meningioma 1 (MN1) gene is a transcriptional co-regulator implicated in other malignancies, albeit its signi...

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Autores principales: Saini, Masum, Jha, Ajaya Nand, Tangri, Rajiv, Qudratullah, Md, Ali, Sher
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788295/
https://www.ncbi.nlm.nih.gov/pubmed/33105486
http://dx.doi.org/10.1093/hmg/ddaa231
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author Saini, Masum
Jha, Ajaya Nand
Tangri, Rajiv
Qudratullah, Md
Ali, Sher
author_facet Saini, Masum
Jha, Ajaya Nand
Tangri, Rajiv
Qudratullah, Md
Ali, Sher
author_sort Saini, Masum
collection PubMed
description Gliomas have substantial mortality to incidence rate ratio and a dismal clinical course. Newer molecular insights, therefore, are imperative to refine glioma diagnosis, prognosis and therapy. Meningioma 1 (MN1) gene is a transcriptional co-regulator implicated in other malignancies, albeit its significance in glioma pathology remains to be explored. IGFBP5 is regulated transcriptionally by MN1 and IGF1 and is associated with higher glioma grade and shorter survival time, prompting us to ascertain their correlation in these tumors. We quantified the expression of MN1, IGFBP5 and IGF1 in 40 glioma samples and examined their interrelatedness. MN1 mRNA-protein inter-correlation and the gene’s copy number were evaluated in these tumors. Publicly available TCGA datasets were used to examine the association of MN1 expression levels with patient survival and for validating our findings. We observed MN1 overexpression correlated with low-grade (LGGs) and not high-grade gliomas and is not determined by the copy number alteration of the gene. Notably, gliomas with upregulated MN1 have better overall survival (OS) and progression-free survival (PFS). IGFBP5 expression associated inversely with MN1 expression levels in gliomas but correlated positively with IGF1 expression in only LGGs. This suggests a potential grade-specific interplay between repressive and activating roles of MN1 and IGF1, respectively, in the regulation of IGFBP5. Thus, MN1 overexpression, a promising predictor of OS and PFS in gliomas, may serve as a prognostic biomarker in clinical practice to categorize patients with survival advantage.
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spelling pubmed-77882952021-01-12 MN1 overexpression with varying tumor grade is a promising predictor of survival of glioma patients Saini, Masum Jha, Ajaya Nand Tangri, Rajiv Qudratullah, Md Ali, Sher Hum Mol Genet General Article Gliomas have substantial mortality to incidence rate ratio and a dismal clinical course. Newer molecular insights, therefore, are imperative to refine glioma diagnosis, prognosis and therapy. Meningioma 1 (MN1) gene is a transcriptional co-regulator implicated in other malignancies, albeit its significance in glioma pathology remains to be explored. IGFBP5 is regulated transcriptionally by MN1 and IGF1 and is associated with higher glioma grade and shorter survival time, prompting us to ascertain their correlation in these tumors. We quantified the expression of MN1, IGFBP5 and IGF1 in 40 glioma samples and examined their interrelatedness. MN1 mRNA-protein inter-correlation and the gene’s copy number were evaluated in these tumors. Publicly available TCGA datasets were used to examine the association of MN1 expression levels with patient survival and for validating our findings. We observed MN1 overexpression correlated with low-grade (LGGs) and not high-grade gliomas and is not determined by the copy number alteration of the gene. Notably, gliomas with upregulated MN1 have better overall survival (OS) and progression-free survival (PFS). IGFBP5 expression associated inversely with MN1 expression levels in gliomas but correlated positively with IGF1 expression in only LGGs. This suggests a potential grade-specific interplay between repressive and activating roles of MN1 and IGF1, respectively, in the regulation of IGFBP5. Thus, MN1 overexpression, a promising predictor of OS and PFS in gliomas, may serve as a prognostic biomarker in clinical practice to categorize patients with survival advantage. Oxford University Press 2020-10-26 /pmc/articles/PMC7788295/ /pubmed/33105486 http://dx.doi.org/10.1093/hmg/ddaa231 Text en © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle General Article
Saini, Masum
Jha, Ajaya Nand
Tangri, Rajiv
Qudratullah, Md
Ali, Sher
MN1 overexpression with varying tumor grade is a promising predictor of survival of glioma patients
title MN1 overexpression with varying tumor grade is a promising predictor of survival of glioma patients
title_full MN1 overexpression with varying tumor grade is a promising predictor of survival of glioma patients
title_fullStr MN1 overexpression with varying tumor grade is a promising predictor of survival of glioma patients
title_full_unstemmed MN1 overexpression with varying tumor grade is a promising predictor of survival of glioma patients
title_short MN1 overexpression with varying tumor grade is a promising predictor of survival of glioma patients
title_sort mn1 overexpression with varying tumor grade is a promising predictor of survival of glioma patients
topic General Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788295/
https://www.ncbi.nlm.nih.gov/pubmed/33105486
http://dx.doi.org/10.1093/hmg/ddaa231
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