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Bioinformatics analysis of high-throughput data to validate potential novel biomarkers and small molecule drugs for glioblastoma multiforme

OBJECTIVE: There have been no recent improvements in the glioblastoma multiforme (GBM) outcome, with median survival remaining 15 months. Consequently, the need to identify novel biomarkers for GBM diagnosis and prognosis, and to develop targeted therapies is high. This study aimed to establish biom...

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Detalles Bibliográficos
Autores principales: Qi, Fuwei, Li, Qing, Lu, Xiaojun, Chen, Zhihua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343367/
https://www.ncbi.nlm.nih.gov/pubmed/32634050
http://dx.doi.org/10.1177/0300060520924541
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author Qi, Fuwei
Li, Qing
Lu, Xiaojun
Chen, Zhihua
author_facet Qi, Fuwei
Li, Qing
Lu, Xiaojun
Chen, Zhihua
author_sort Qi, Fuwei
collection PubMed
description OBJECTIVE: There have been no recent improvements in the glioblastoma multiforme (GBM) outcome, with median survival remaining 15 months. Consequently, the need to identify novel biomarkers for GBM diagnosis and prognosis, and to develop targeted therapies is high. This study aimed to establish biomarkers for GBM pathogenesis and prognosis. METHODS: In total, 220 overlapping differentially expressed genes (DEGs) were obtained by integrating four microarray datasets from the Gene Expression Omnibus database (GSE4290, GSE12657, GSE15824, and GSE68848). Then a 140-node protein–protein interaction network with 343 interactions was constructed. RESULTS: The immune response and cell adhesion molecules were the most significantly enriched functions and pathways, respectively, among DEGs. The designated hub genes ITGB5 and RGS4, which have a high degree of connectivity, were closely correlated with patient prognosis, and GEPIA database mining further confirmed their differential expression in GBM versus normal tissue. We also determined the 20 most appropriate small molecules that could potentially reverse GBM gene expression, Prestwick-1080 was the most promising and had the highest negative scores. CONCLUSIONS: This study identified ITGB5 and RGS4 as potential biomarkers for GBM diagnosis and prognosis. Insights into molecular mechanisms governing GBM occurrence and progression will help identify alternative biomarkers for clinical practice.
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spelling pubmed-73433672020-07-17 Bioinformatics analysis of high-throughput data to validate potential novel biomarkers and small molecule drugs for glioblastoma multiforme Qi, Fuwei Li, Qing Lu, Xiaojun Chen, Zhihua J Int Med Res Pre-Clinical Research Report OBJECTIVE: There have been no recent improvements in the glioblastoma multiforme (GBM) outcome, with median survival remaining 15 months. Consequently, the need to identify novel biomarkers for GBM diagnosis and prognosis, and to develop targeted therapies is high. This study aimed to establish biomarkers for GBM pathogenesis and prognosis. METHODS: In total, 220 overlapping differentially expressed genes (DEGs) were obtained by integrating four microarray datasets from the Gene Expression Omnibus database (GSE4290, GSE12657, GSE15824, and GSE68848). Then a 140-node protein–protein interaction network with 343 interactions was constructed. RESULTS: The immune response and cell adhesion molecules were the most significantly enriched functions and pathways, respectively, among DEGs. The designated hub genes ITGB5 and RGS4, which have a high degree of connectivity, were closely correlated with patient prognosis, and GEPIA database mining further confirmed their differential expression in GBM versus normal tissue. We also determined the 20 most appropriate small molecules that could potentially reverse GBM gene expression, Prestwick-1080 was the most promising and had the highest negative scores. CONCLUSIONS: This study identified ITGB5 and RGS4 as potential biomarkers for GBM diagnosis and prognosis. Insights into molecular mechanisms governing GBM occurrence and progression will help identify alternative biomarkers for clinical practice. SAGE Publications 2020-07-07 /pmc/articles/PMC7343367/ /pubmed/32634050 http://dx.doi.org/10.1177/0300060520924541 Text en © The Author(s) 2020 https://creativecommons.org/licenses/by-nc/4.0/ Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Pre-Clinical Research Report
Qi, Fuwei
Li, Qing
Lu, Xiaojun
Chen, Zhihua
Bioinformatics analysis of high-throughput data to validate potential novel biomarkers and small molecule drugs for glioblastoma multiforme
title Bioinformatics analysis of high-throughput data to validate potential novel biomarkers and small molecule drugs for glioblastoma multiforme
title_full Bioinformatics analysis of high-throughput data to validate potential novel biomarkers and small molecule drugs for glioblastoma multiforme
title_fullStr Bioinformatics analysis of high-throughput data to validate potential novel biomarkers and small molecule drugs for glioblastoma multiforme
title_full_unstemmed Bioinformatics analysis of high-throughput data to validate potential novel biomarkers and small molecule drugs for glioblastoma multiforme
title_short Bioinformatics analysis of high-throughput data to validate potential novel biomarkers and small molecule drugs for glioblastoma multiforme
title_sort bioinformatics analysis of high-throughput data to validate potential novel biomarkers and small molecule drugs for glioblastoma multiforme
topic Pre-Clinical Research Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343367/
https://www.ncbi.nlm.nih.gov/pubmed/32634050
http://dx.doi.org/10.1177/0300060520924541
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