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Identification and validation of a 17-gene signature to improve the survival prediction of gliomas

Gliomas are one of the most frequent types of nervous system tumours and have significant morbidity and mortality rates. As a result, it is critical to fully comprehend the molecular mechanism of glioma to predict prognosis and target gene therapy. The goal of this research was to discover the hub g...

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Autores principales: Tong, Shiao, Xia, Minqi, Xu, Yang, Sun, Qian, Ye, Liguo, Cai, Jiayang, Ye, Zhang, Tian, Daofeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9556650/
https://www.ncbi.nlm.nih.gov/pubmed/36248799
http://dx.doi.org/10.3389/fimmu.2022.1000396
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author Tong, Shiao
Xia, Minqi
Xu, Yang
Sun, Qian
Ye, Liguo
Cai, Jiayang
Ye, Zhang
Tian, Daofeng
author_facet Tong, Shiao
Xia, Minqi
Xu, Yang
Sun, Qian
Ye, Liguo
Cai, Jiayang
Ye, Zhang
Tian, Daofeng
author_sort Tong, Shiao
collection PubMed
description Gliomas are one of the most frequent types of nervous system tumours and have significant morbidity and mortality rates. As a result, it is critical to fully comprehend the molecular mechanism of glioma to predict prognosis and target gene therapy. The goal of this research was to discover the hub genes of glioma and investigate their prognostic and diagnostic usefulness. In this study, we collected mRNA expression profiles and clinical information from glioma patients in the TCGA, GTEx, GSE68848, and GSE4920 databases. WGCNA and differential expression analysis identified 170 DEGs in the collected datasets. GO and KEGG pathway analyses revealed that DEGs were mainly enriched in gliogenesis and extracellular matrix. LASSO was performed to construct prognostic signatures in the TCGA cohort, and 17 genes were used to build risk models and were validated in the CGGA database. The ROC curve confirmed the accuracy of the prognostic signature. Univariate and multivariate Cox regression analyses showed that all independent risk factors for glioma except gender. Next, we performed ssGSEA to demonstrate a high correlation between risk score and immunity. Subsequently, 7 hub genes were identified by the PPI network and found to have great drug targeting potential. Finally, RPL39, as one of the hub genes, was found to be closely related to the prognosis of glioma patients. Knockdown of RPL39 in vitro significantly inhibited the proliferation and migration of glioma cells, whereas overexpression of RPL39 had the opposite effect. And we found that knockdown of RPL39 inhibited the polarization and infiltration of M2 phenotype macrophages. In conclusion, our new prognosis-related model provides more potential therapeutic strategies for glioma patients.
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spelling pubmed-95566502022-10-14 Identification and validation of a 17-gene signature to improve the survival prediction of gliomas Tong, Shiao Xia, Minqi Xu, Yang Sun, Qian Ye, Liguo Cai, Jiayang Ye, Zhang Tian, Daofeng Front Immunol Immunology Gliomas are one of the most frequent types of nervous system tumours and have significant morbidity and mortality rates. As a result, it is critical to fully comprehend the molecular mechanism of glioma to predict prognosis and target gene therapy. The goal of this research was to discover the hub genes of glioma and investigate their prognostic and diagnostic usefulness. In this study, we collected mRNA expression profiles and clinical information from glioma patients in the TCGA, GTEx, GSE68848, and GSE4920 databases. WGCNA and differential expression analysis identified 170 DEGs in the collected datasets. GO and KEGG pathway analyses revealed that DEGs were mainly enriched in gliogenesis and extracellular matrix. LASSO was performed to construct prognostic signatures in the TCGA cohort, and 17 genes were used to build risk models and were validated in the CGGA database. The ROC curve confirmed the accuracy of the prognostic signature. Univariate and multivariate Cox regression analyses showed that all independent risk factors for glioma except gender. Next, we performed ssGSEA to demonstrate a high correlation between risk score and immunity. Subsequently, 7 hub genes were identified by the PPI network and found to have great drug targeting potential. Finally, RPL39, as one of the hub genes, was found to be closely related to the prognosis of glioma patients. Knockdown of RPL39 in vitro significantly inhibited the proliferation and migration of glioma cells, whereas overexpression of RPL39 had the opposite effect. And we found that knockdown of RPL39 inhibited the polarization and infiltration of M2 phenotype macrophages. In conclusion, our new prognosis-related model provides more potential therapeutic strategies for glioma patients. Frontiers Media S.A. 2022-09-29 /pmc/articles/PMC9556650/ /pubmed/36248799 http://dx.doi.org/10.3389/fimmu.2022.1000396 Text en Copyright © 2022 Tong, Xia, Xu, Sun, Ye, Cai, Ye and Tian https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Tong, Shiao
Xia, Minqi
Xu, Yang
Sun, Qian
Ye, Liguo
Cai, Jiayang
Ye, Zhang
Tian, Daofeng
Identification and validation of a 17-gene signature to improve the survival prediction of gliomas
title Identification and validation of a 17-gene signature to improve the survival prediction of gliomas
title_full Identification and validation of a 17-gene signature to improve the survival prediction of gliomas
title_fullStr Identification and validation of a 17-gene signature to improve the survival prediction of gliomas
title_full_unstemmed Identification and validation of a 17-gene signature to improve the survival prediction of gliomas
title_short Identification and validation of a 17-gene signature to improve the survival prediction of gliomas
title_sort identification and validation of a 17-gene signature to improve the survival prediction of gliomas
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9556650/
https://www.ncbi.nlm.nih.gov/pubmed/36248799
http://dx.doi.org/10.3389/fimmu.2022.1000396
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