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Eleven genes associated with progression and prognosis of endometrial cancer (EC) identified by comprehensive bioinformatics analysis

BACKGROUND: Endometrial cancer (EC) is one of the female malignant tumors. Endometrial cancer predominately affects post-menopausal women. Bioinformatics analysis has been widely applied to screen and analyze genes in linkage to various types of cancer progression. METHODS: Download the gene express...

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Autores principales: Liu, JinHui, Zhou, ShuLin, Li, SiYue, Jiang, Yi, Wan, YiCong, Ma, XiaoLing, Cheng, WenJun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6528324/
https://www.ncbi.nlm.nih.gov/pubmed/31139013
http://dx.doi.org/10.1186/s12935-019-0859-1
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author Liu, JinHui
Zhou, ShuLin
Li, SiYue
Jiang, Yi
Wan, YiCong
Ma, XiaoLing
Cheng, WenJun
author_facet Liu, JinHui
Zhou, ShuLin
Li, SiYue
Jiang, Yi
Wan, YiCong
Ma, XiaoLing
Cheng, WenJun
author_sort Liu, JinHui
collection PubMed
description BACKGROUND: Endometrial cancer (EC) is one of the female malignant tumors. Endometrial cancer predominately affects post-menopausal women. Bioinformatics analysis has been widely applied to screen and analyze genes in linkage to various types of cancer progression. METHODS: Download the gene expression profile from Gene Expression Omnibus (GEO). Calculate raw expression data according to pre-processing procedures. We performed the “limma” R language package to screen DEGs between Endometrial cancer tissue samples and normal uterus tissue samples. Enrichment of the functions and pathways was analyzed by using clusterprofiler. We utilized Search Tool for the Retrieval of Interacting Genes Database (STRING) to assess protein–protein interaction (PPI) information, and then we used plug-in Molecular Complex Detection (MCODE) to screen hub modules of PPI network in Cytoscape. We also performed functional analysis on the genes in the hub module by using clusterprofiler. Next, we utilized the “WGCNA” package in R to establish co-expression network for the DEGs. The Venn diagram was performed to overlap the gene in key module and hub PPI cluster. We validated the key genes in TCGA, GEPIA, UALCAN and Immunohistochemistry staining obtained from The Human Protein Atlas database. And then we did ROC curve analysis by SPSS. Gene set enrichment analysis (GSEA) and mutation analysis were also performed for hub genes. RESULTS: Functional and pathway enrichment analysis demonstrated that the upregulated differentially expressed genes (DEGs) were significantly enriched in CXCR chemokine receptor binding, chemokine activity, chemokine receptor binding, G-protein coupled receptor binding, RAGE receptor binding, cytokine activity, microtubule binding, receptor regulator activity and microtubule motor activity, and the down-regulated genes were highly enriched in collagen binding. After using STRING software to construct PPI network, 30 prominent proteins were identified and the first two significant modules were selected. In co-expression network, 5 EC-related modules were identified. Among them, the turquoise module has the highest correlation with the EC. We further analyzed the genes in the PPI and turquoise module, and selected eleven key genes related to EC after validation of TCGA database, GEPIA, UALCAN and immunohistochemistry. Six of them had mutation significance. CONCLUSIONS: In summary, these 11 genes may become new therapy targets for EC treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12935-019-0859-1) contains supplementary material, which is available to authorized users.
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spelling pubmed-65283242019-05-28 Eleven genes associated with progression and prognosis of endometrial cancer (EC) identified by comprehensive bioinformatics analysis Liu, JinHui Zhou, ShuLin Li, SiYue Jiang, Yi Wan, YiCong Ma, XiaoLing Cheng, WenJun Cancer Cell Int Primary Research BACKGROUND: Endometrial cancer (EC) is one of the female malignant tumors. Endometrial cancer predominately affects post-menopausal women. Bioinformatics analysis has been widely applied to screen and analyze genes in linkage to various types of cancer progression. METHODS: Download the gene expression profile from Gene Expression Omnibus (GEO). Calculate raw expression data according to pre-processing procedures. We performed the “limma” R language package to screen DEGs between Endometrial cancer tissue samples and normal uterus tissue samples. Enrichment of the functions and pathways was analyzed by using clusterprofiler. We utilized Search Tool for the Retrieval of Interacting Genes Database (STRING) to assess protein–protein interaction (PPI) information, and then we used plug-in Molecular Complex Detection (MCODE) to screen hub modules of PPI network in Cytoscape. We also performed functional analysis on the genes in the hub module by using clusterprofiler. Next, we utilized the “WGCNA” package in R to establish co-expression network for the DEGs. The Venn diagram was performed to overlap the gene in key module and hub PPI cluster. We validated the key genes in TCGA, GEPIA, UALCAN and Immunohistochemistry staining obtained from The Human Protein Atlas database. And then we did ROC curve analysis by SPSS. Gene set enrichment analysis (GSEA) and mutation analysis were also performed for hub genes. RESULTS: Functional and pathway enrichment analysis demonstrated that the upregulated differentially expressed genes (DEGs) were significantly enriched in CXCR chemokine receptor binding, chemokine activity, chemokine receptor binding, G-protein coupled receptor binding, RAGE receptor binding, cytokine activity, microtubule binding, receptor regulator activity and microtubule motor activity, and the down-regulated genes were highly enriched in collagen binding. After using STRING software to construct PPI network, 30 prominent proteins were identified and the first two significant modules were selected. In co-expression network, 5 EC-related modules were identified. Among them, the turquoise module has the highest correlation with the EC. We further analyzed the genes in the PPI and turquoise module, and selected eleven key genes related to EC after validation of TCGA database, GEPIA, UALCAN and immunohistochemistry. Six of them had mutation significance. CONCLUSIONS: In summary, these 11 genes may become new therapy targets for EC treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12935-019-0859-1) contains supplementary material, which is available to authorized users. BioMed Central 2019-05-20 /pmc/articles/PMC6528324/ /pubmed/31139013 http://dx.doi.org/10.1186/s12935-019-0859-1 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Primary Research
Liu, JinHui
Zhou, ShuLin
Li, SiYue
Jiang, Yi
Wan, YiCong
Ma, XiaoLing
Cheng, WenJun
Eleven genes associated with progression and prognosis of endometrial cancer (EC) identified by comprehensive bioinformatics analysis
title Eleven genes associated with progression and prognosis of endometrial cancer (EC) identified by comprehensive bioinformatics analysis
title_full Eleven genes associated with progression and prognosis of endometrial cancer (EC) identified by comprehensive bioinformatics analysis
title_fullStr Eleven genes associated with progression and prognosis of endometrial cancer (EC) identified by comprehensive bioinformatics analysis
title_full_unstemmed Eleven genes associated with progression and prognosis of endometrial cancer (EC) identified by comprehensive bioinformatics analysis
title_short Eleven genes associated with progression and prognosis of endometrial cancer (EC) identified by comprehensive bioinformatics analysis
title_sort eleven genes associated with progression and prognosis of endometrial cancer (ec) identified by comprehensive bioinformatics analysis
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6528324/
https://www.ncbi.nlm.nih.gov/pubmed/31139013
http://dx.doi.org/10.1186/s12935-019-0859-1
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