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...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Chuang, Yu, Ruoxi, Li, Zhi, Song, Huicong, Zang, Dan, Deng, Mingming, Fan, Yibo, Liu, Yunpeng, Zhang, Ye, Qu, Xiujuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2019
Materias:
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
_version_ 1783424390822625280
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
work_keys_str_mv AT zhangchuang comprehensiveanalysisofgenesbasedonchr1p19qcodeletionrevealsarobust4geneprognosticsignatureforlowergradeglioma
AT yuruoxi comprehensiveanalysisofgenesbasedonchr1p19qcodeletionrevealsarobust4geneprognosticsignatureforlowergradeglioma
AT lizhi comprehensiveanalysisofgenesbasedonchr1p19qcodeletionrevealsarobust4geneprognosticsignatureforlowergradeglioma
AT songhuicong comprehensiveanalysisofgenesbasedonchr1p19qcodeletionrevealsarobust4geneprognosticsignatureforlowergradeglioma
AT zangdan comprehensiveanalysisofgenesbasedonchr1p19qcodeletionrevealsarobust4geneprognosticsignatureforlowergradeglioma
AT dengmingming comprehensiveanalysisofgenesbasedonchr1p19qcodeletionrevealsarobust4geneprognosticsignatureforlowergradeglioma
AT fanyibo comprehensiveanalysisofgenesbasedonchr1p19qcodeletionrevealsarobust4geneprognosticsignatureforlowergradeglioma
AT liuyunpeng comprehensiveanalysisofgenesbasedonchr1p19qcodeletionrevealsarobust4geneprognosticsignatureforlowergradeglioma
AT zhangye comprehensiveanalysisofgenesbasedonchr1p19qcodeletionrevealsarobust4geneprognosticsignatureforlowergradeglioma
AT quxiujuan comprehensiveanalysisofgenesbasedonchr1p19qcodeletionrevealsarobust4geneprognosticsignatureforlowergradeglioma