Comprehensive analysis of genes based on chr1p/19q co-deletion reveals a robust 4-gene prognostic signature for lower grade glioma
Purpose: The chr1p/19q co-deletion is a favorable prognostic factor in patients with lower grade glioma. The aim of this study was to reveal key genes for prognosis and establish prognostic gene signatures based on genes encoded by chr1p/19q. Materials and methods: The data was downloaded from The C...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Dove
2019
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6551448/ https://www.ncbi.nlm.nih.gov/pubmed/31213913 http://dx.doi.org/10.2147/CMAR.S199396 |
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author | Zhang, Chuang Yu, Ruoxi Li, Zhi Song, Huicong Zang, Dan Deng, Mingming Fan, Yibo Liu, Yunpeng Zhang, Ye Qu, Xiujuan |
author_facet | Zhang, Chuang Yu, Ruoxi Li, Zhi Song, Huicong Zang, Dan Deng, Mingming Fan, Yibo Liu, Yunpeng Zhang, Ye Qu, Xiujuan |
author_sort | Zhang, Chuang |
collection | PubMed |
description | Purpose: The chr1p/19q co-deletion is a favorable prognostic factor in patients with lower grade glioma. The aim of this study was to reveal key genes for prognosis and establish prognostic gene signatures based on genes encoded by chr1p/19q. Materials and methods: The data was downloaded from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA) and Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) between lower grade glioma tissue and normal brain were identified. The univariate COX regression, robust likelihood-base survival analysis (rbsurv) and multivariate COX regression analysis were used to establish the 4-gene-signature based on the DEGs. The receiver operating characteristic (ROC) curve and the Kaplan-Mere curve were used to verify the prediction accuracy of the signature. Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were also performed to explore the reasons for good prognosis in patients with chr1p/19q deletion. Results: A total of 1346 DEGs were identified between lower grade glioma samples and normal brain samples in GSE16011, including 56 up-regulated mRNAs located on chr1p and 20 up-regulated mRNAs located on chr19q. We established a 4-gene-signature that was significantly associated with survival based on the 76 gene. The AUC of the 4-gene-signature for 5-year OS in TCGA and CGGA was 0.837 and 0.876, respectively, which was superior compared to other parameters such as chr1p/19q co-deletion, IDH mutant, WHO grade and histology type, especially in chr1p/19q non-co-deletion patients. GSEA and KEGG analysis suggested that the prolongation of chr1p/19q in patients could be associated with cell cycle and DNA mismatch repairing. Conclusions: We established a robust 4-gene-signature based on the chr1p/19q and we explored the potential function of these newly identified survival-associated genes by bioinformatics analysis. The 4-gene from the signature are promising molecular targets to be used in the future. |
format | Online Article Text |
id | pubmed-6551448 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-65514482019-06-18 Comprehensive analysis of genes based on chr1p/19q co-deletion reveals a robust 4-gene prognostic signature for lower grade glioma Zhang, Chuang Yu, Ruoxi Li, Zhi Song, Huicong Zang, Dan Deng, Mingming Fan, Yibo Liu, Yunpeng Zhang, Ye Qu, Xiujuan Cancer Manag Res Original Research Purpose: The chr1p/19q co-deletion is a favorable prognostic factor in patients with lower grade glioma. The aim of this study was to reveal key genes for prognosis and establish prognostic gene signatures based on genes encoded by chr1p/19q. Materials and methods: The data was downloaded from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA) and Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) between lower grade glioma tissue and normal brain were identified. The univariate COX regression, robust likelihood-base survival analysis (rbsurv) and multivariate COX regression analysis were used to establish the 4-gene-signature based on the DEGs. The receiver operating characteristic (ROC) curve and the Kaplan-Mere curve were used to verify the prediction accuracy of the signature. Gene Set Enrichment Analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were also performed to explore the reasons for good prognosis in patients with chr1p/19q deletion. Results: A total of 1346 DEGs were identified between lower grade glioma samples and normal brain samples in GSE16011, including 56 up-regulated mRNAs located on chr1p and 20 up-regulated mRNAs located on chr19q. We established a 4-gene-signature that was significantly associated with survival based on the 76 gene. The AUC of the 4-gene-signature for 5-year OS in TCGA and CGGA was 0.837 and 0.876, respectively, which was superior compared to other parameters such as chr1p/19q co-deletion, IDH mutant, WHO grade and histology type, especially in chr1p/19q non-co-deletion patients. GSEA and KEGG analysis suggested that the prolongation of chr1p/19q in patients could be associated with cell cycle and DNA mismatch repairing. Conclusions: We established a robust 4-gene-signature based on the chr1p/19q and we explored the potential function of these newly identified survival-associated genes by bioinformatics analysis. The 4-gene from the signature are promising molecular targets to be used in the future. Dove 2019-05-29 /pmc/articles/PMC6551448/ /pubmed/31213913 http://dx.doi.org/10.2147/CMAR.S199396 Text en © 2019 Zhang et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Zhang, Chuang Yu, Ruoxi Li, Zhi Song, Huicong Zang, Dan Deng, Mingming Fan, Yibo Liu, Yunpeng Zhang, Ye Qu, Xiujuan Comprehensive analysis of genes based on chr1p/19q co-deletion reveals a robust 4-gene prognostic signature for lower grade glioma |
title | Comprehensive analysis of genes based on chr1p/19q co-deletion reveals a robust 4-gene prognostic signature for lower grade glioma |
title_full | Comprehensive analysis of genes based on chr1p/19q co-deletion reveals a robust 4-gene prognostic signature for lower grade glioma |
title_fullStr | Comprehensive analysis of genes based on chr1p/19q co-deletion reveals a robust 4-gene prognostic signature for lower grade glioma |
title_full_unstemmed | Comprehensive analysis of genes based on chr1p/19q co-deletion reveals a robust 4-gene prognostic signature for lower grade glioma |
title_short | Comprehensive analysis of genes based on chr1p/19q co-deletion reveals a robust 4-gene prognostic signature for lower grade glioma |
title_sort | comprehensive analysis of genes based on chr1p/19q co-deletion reveals a robust 4-gene prognostic signature for lower grade glioma |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6551448/ https://www.ncbi.nlm.nih.gov/pubmed/31213913 http://dx.doi.org/10.2147/CMAR.S199396 |
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