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Bioinformatics analysis of molecular genetic targets and key pathways for hepatocellular carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC) is the second leading cause of death among cancers worldwide. In this study, we aimed to identify the molecular target genes and detect the key mechanisms of HCC. Three gene expression profiles (GSE84006, GSE14323, GSE14811) and two miRNA expression profile...

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Autores principales: Tu, Junxue, Chen, Jingjing, He, Meimei, Tong, Hongfei, Liu, Haibin, Zhou, Bin, Liao, Yi, Wang, Zhaohong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6612290/
https://www.ncbi.nlm.nih.gov/pubmed/31303768
http://dx.doi.org/10.2147/OTT.S198802
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author Tu, Junxue
Chen, Jingjing
He, Meimei
Tong, Hongfei
Liu, Haibin
Zhou, Bin
Liao, Yi
Wang, Zhaohong
author_facet Tu, Junxue
Chen, Jingjing
He, Meimei
Tong, Hongfei
Liu, Haibin
Zhou, Bin
Liao, Yi
Wang, Zhaohong
author_sort Tu, Junxue
collection PubMed
description BACKGROUND: Hepatocellular carcinoma (HCC) is the second leading cause of death among cancers worldwide. In this study, we aimed to identify the molecular target genes and detect the key mechanisms of HCC. Three gene expression profiles (GSE84006, GSE14323, GSE14811) and two miRNA expression profiles (GSE40744, GSE36915) were analyzed to determine the molecular target genes, microRNAs (miRNAs) and the potential molecular mechanisms in HCC. METHODS: All profiles were extracted from the Gene Expression Omnibus database. The identification of the differentially expressed genes (DEGs) was analyzed by the GEO2R method. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and gene ontology (GO) enrichment analysis performed database for Integrated Discovery, Visualization and Annotation. The miRNA-gene network and protein–protein interaction (PPI) network were correlated by the Cytoscape software. The key target genes were identified by the CytoHubba plugin, Molecular Complex Detection (MCODE) plugin and miRNA-gene network. The identified hub genes were testified for survival curve using the Kaplan–Meier plotter database. RESULTS: Expression profiles had 592 overlapped DEGs. The majority of the DEGs were enriched in membrane-bounded organelles and intracellular membrane-bounded organelles. These DEGs were significantly enriched in metabolic, protein processing in the endoplasmic reticulum and thyroid cancer pathways. PPI network analysis showed these genes were mostly involved in the pathogenic Escherichia coli infection and the regulation of actin cytoskeleton pathways. Combining these results, we identified 10 key genes involving in the progression of HCC. Finally, PLK1, PRCC, PRPF4 and PSMA7 exhibited higher expression levels in HCC patients with poor prognosis than those for lower expression via Kaplan–Meier plotter database. CONCLUSION: PLK1, PRCC, PRPF4 and PSMA7 could be potential biomarkers or therapeutic targets for HCC. Meanwhile, the metabolic pathway, protein processing in the endoplasmic reticulum and the thyroid cancer pathway may play vital roles in the progression of HCC.
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spelling pubmed-66122902019-07-14 Bioinformatics analysis of molecular genetic targets and key pathways for hepatocellular carcinoma Tu, Junxue Chen, Jingjing He, Meimei Tong, Hongfei Liu, Haibin Zhou, Bin Liao, Yi Wang, Zhaohong Onco Targets Ther Original Research BACKGROUND: Hepatocellular carcinoma (HCC) is the second leading cause of death among cancers worldwide. In this study, we aimed to identify the molecular target genes and detect the key mechanisms of HCC. Three gene expression profiles (GSE84006, GSE14323, GSE14811) and two miRNA expression profiles (GSE40744, GSE36915) were analyzed to determine the molecular target genes, microRNAs (miRNAs) and the potential molecular mechanisms in HCC. METHODS: All profiles were extracted from the Gene Expression Omnibus database. The identification of the differentially expressed genes (DEGs) was analyzed by the GEO2R method. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and gene ontology (GO) enrichment analysis performed database for Integrated Discovery, Visualization and Annotation. The miRNA-gene network and protein–protein interaction (PPI) network were correlated by the Cytoscape software. The key target genes were identified by the CytoHubba plugin, Molecular Complex Detection (MCODE) plugin and miRNA-gene network. The identified hub genes were testified for survival curve using the Kaplan–Meier plotter database. RESULTS: Expression profiles had 592 overlapped DEGs. The majority of the DEGs were enriched in membrane-bounded organelles and intracellular membrane-bounded organelles. These DEGs were significantly enriched in metabolic, protein processing in the endoplasmic reticulum and thyroid cancer pathways. PPI network analysis showed these genes were mostly involved in the pathogenic Escherichia coli infection and the regulation of actin cytoskeleton pathways. Combining these results, we identified 10 key genes involving in the progression of HCC. Finally, PLK1, PRCC, PRPF4 and PSMA7 exhibited higher expression levels in HCC patients with poor prognosis than those for lower expression via Kaplan–Meier plotter database. CONCLUSION: PLK1, PRCC, PRPF4 and PSMA7 could be potential biomarkers or therapeutic targets for HCC. Meanwhile, the metabolic pathway, protein processing in the endoplasmic reticulum and the thyroid cancer pathway may play vital roles in the progression of HCC. Dove 2019-07-02 /pmc/articles/PMC6612290/ /pubmed/31303768 http://dx.doi.org/10.2147/OTT.S198802 Text en © 2019 Tu 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
Tu, Junxue
Chen, Jingjing
He, Meimei
Tong, Hongfei
Liu, Haibin
Zhou, Bin
Liao, Yi
Wang, Zhaohong
Bioinformatics analysis of molecular genetic targets and key pathways for hepatocellular carcinoma
title Bioinformatics analysis of molecular genetic targets and key pathways for hepatocellular carcinoma
title_full Bioinformatics analysis of molecular genetic targets and key pathways for hepatocellular carcinoma
title_fullStr Bioinformatics analysis of molecular genetic targets and key pathways for hepatocellular carcinoma
title_full_unstemmed Bioinformatics analysis of molecular genetic targets and key pathways for hepatocellular carcinoma
title_short Bioinformatics analysis of molecular genetic targets and key pathways for hepatocellular carcinoma
title_sort bioinformatics analysis of molecular genetic targets and key pathways for hepatocellular carcinoma
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6612290/
https://www.ncbi.nlm.nih.gov/pubmed/31303768
http://dx.doi.org/10.2147/OTT.S198802
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