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A Prognostic Nomogram Model Based on mRNA Expression of DNA Methylation-Driven Genes for Gastric Cancer

PURPOSE: The exploration and interpretation of DNA methylation-driven genes might contribute to molecular classification, prognostic prediction and therapeutic choice. In this study, we built a prognostic risk model via integrating analysis of the transcriptome and methylation profile for patients w...

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Autores principales: Chen, Zuhua, Liu, Bo, Yi, Minxiao, Qiu, Hong, Yuan, Xianglin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732649/
https://www.ncbi.nlm.nih.gov/pubmed/33330065
http://dx.doi.org/10.3389/fonc.2020.584733
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author Chen, Zuhua
Liu, Bo
Yi, Minxiao
Qiu, Hong
Yuan, Xianglin
author_facet Chen, Zuhua
Liu, Bo
Yi, Minxiao
Qiu, Hong
Yuan, Xianglin
author_sort Chen, Zuhua
collection PubMed
description PURPOSE: The exploration and interpretation of DNA methylation-driven genes might contribute to molecular classification, prognostic prediction and therapeutic choice. In this study, we built a prognostic risk model via integrating analysis of the transcriptome and methylation profile for patients with gastric cancer (GC). METHODS: The mRNA expression profiles, DNA methylation profiles and corresponding clinicopathological information of 415 GC patients were downloaded from The Cancer Genome Atlas (TCGA). Differential expression and correlation analysis were performed to identify DNA methylation-driven genes. The candidate genes were selected by univariate Cox regression analyses followed by the least absolute shrinkage and selection operator (LASSO) regression. A prognostic risk nomogram model was then built together with clinicopathological parameters. RESULTS: 5 DNA methylation-driven genes (CXCL3, F5, GNAI1, GAMT and GHR) were identified by integrated analyses and selected to construct the prognostic risk model with clinicopathological parameters. High expression and low DNA hypermethylation of F5, GNAI1, GAMT and GHR, as well as low expression and high DNA hypomethylation of CXCL3 were significantly associated with poor prognosis rates, respectively. The high-risk group showed a significantly shorter prognosis than the low-risk group in the TCGA dataset (HR = 0.212, 95% CI = 0.139–0.322, P = 2e-15). The final nomogram model showed high predictive efficiency and consistency in the training and validation group. CONCLUSION: We construct and validate a prognostic nomogram model for GC based on five DNA methylation-driven genes with high performance and stability. This nomogram model might be a powerful tool for prognosis evaluation in the clinic and also provided novel insights into the epigenetics in GC.
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spelling pubmed-77326492020-12-15 A Prognostic Nomogram Model Based on mRNA Expression of DNA Methylation-Driven Genes for Gastric Cancer Chen, Zuhua Liu, Bo Yi, Minxiao Qiu, Hong Yuan, Xianglin Front Oncol Oncology PURPOSE: The exploration and interpretation of DNA methylation-driven genes might contribute to molecular classification, prognostic prediction and therapeutic choice. In this study, we built a prognostic risk model via integrating analysis of the transcriptome and methylation profile for patients with gastric cancer (GC). METHODS: The mRNA expression profiles, DNA methylation profiles and corresponding clinicopathological information of 415 GC patients were downloaded from The Cancer Genome Atlas (TCGA). Differential expression and correlation analysis were performed to identify DNA methylation-driven genes. The candidate genes were selected by univariate Cox regression analyses followed by the least absolute shrinkage and selection operator (LASSO) regression. A prognostic risk nomogram model was then built together with clinicopathological parameters. RESULTS: 5 DNA methylation-driven genes (CXCL3, F5, GNAI1, GAMT and GHR) were identified by integrated analyses and selected to construct the prognostic risk model with clinicopathological parameters. High expression and low DNA hypermethylation of F5, GNAI1, GAMT and GHR, as well as low expression and high DNA hypomethylation of CXCL3 were significantly associated with poor prognosis rates, respectively. The high-risk group showed a significantly shorter prognosis than the low-risk group in the TCGA dataset (HR = 0.212, 95% CI = 0.139–0.322, P = 2e-15). The final nomogram model showed high predictive efficiency and consistency in the training and validation group. CONCLUSION: We construct and validate a prognostic nomogram model for GC based on five DNA methylation-driven genes with high performance and stability. This nomogram model might be a powerful tool for prognosis evaluation in the clinic and also provided novel insights into the epigenetics in GC. Frontiers Media S.A. 2020-11-24 /pmc/articles/PMC7732649/ /pubmed/33330065 http://dx.doi.org/10.3389/fonc.2020.584733 Text en Copyright © 2020 Chen, Liu, Yi, Qiu and Yuan http://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 Oncology
Chen, Zuhua
Liu, Bo
Yi, Minxiao
Qiu, Hong
Yuan, Xianglin
A Prognostic Nomogram Model Based on mRNA Expression of DNA Methylation-Driven Genes for Gastric Cancer
title A Prognostic Nomogram Model Based on mRNA Expression of DNA Methylation-Driven Genes for Gastric Cancer
title_full A Prognostic Nomogram Model Based on mRNA Expression of DNA Methylation-Driven Genes for Gastric Cancer
title_fullStr A Prognostic Nomogram Model Based on mRNA Expression of DNA Methylation-Driven Genes for Gastric Cancer
title_full_unstemmed A Prognostic Nomogram Model Based on mRNA Expression of DNA Methylation-Driven Genes for Gastric Cancer
title_short A Prognostic Nomogram Model Based on mRNA Expression of DNA Methylation-Driven Genes for Gastric Cancer
title_sort prognostic nomogram model based on mrna expression of dna methylation-driven genes for gastric cancer
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732649/
https://www.ncbi.nlm.nih.gov/pubmed/33330065
http://dx.doi.org/10.3389/fonc.2020.584733
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