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Common gene signatures and key pathways in hypopharyngeal and esophageal squamous cell carcinoma: Evidence from bioinformatic analysis
BACKGROUND: Hypopharyngeal and esophageal squamous cell carcinoma (ESCC) are the most common double primary tumors with poor prognosis. Intensive work has been made to illuminate the etiology, but the common carcinogenic mechanism remains unclear. Thus, we conducted the study to seek to find the com...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571924/ https://www.ncbi.nlm.nih.gov/pubmed/33080677 http://dx.doi.org/10.1097/MD.0000000000022434 |
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author | Zhou, Rui Liu, Denghua Zhu, Jing Zhang, Tao |
author_facet | Zhou, Rui Liu, Denghua Zhu, Jing Zhang, Tao |
author_sort | Zhou, Rui |
collection | PubMed |
description | BACKGROUND: Hypopharyngeal and esophageal squamous cell carcinoma (ESCC) are the most common double primary tumors with poor prognosis. Intensive work has been made to illuminate the etiology, but the common carcinogenic mechanism remains unclear. Thus, we conducted the study to seek to find the common gene signatures and key functional pathways associated with oncogenesis and treatment in hypopharyngeal squamous cell carcinoma (HSCC) and ESCC by bioinformatic analysis. METHODS: Three independent datasets (GSE2379, GSE20347, and GSE75241) were screened out from the Gene Expression Omnibus (GEO) database and the overlapping differentially expressed genes (DEGs) were identified using GEO2R online platform. Subsequently, the Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis of DEGs were conducted using database for annotation, visualization and integrated discovery (DAVID). Meanwhile, the protein–protein interaction network (PPI) constructed by search tool for the retrieval of interacting genes (STRING) was visualized using Cytoscape. Afterwards, the most key module and hub genes were extracted from the PPI network using the Molecular Complex Detection plugin. Moreover, the gene expression profiling interactive analysis (GEPIA) was applied to verify the expression differences and conduct the survival analyses of hub genes. Finally, the interaction network of miRNAs and hub genes constructed by encyclopedia of RNA interactomes (ENCORI) was visualized using Cytoscape. RESULTS: A total of 43 DEGs were identified, comprising 25 upregulated genes and 18 downregulated genes, which were mainly involved in the extracellular matrix-receptor interaction, collagen metabolic, epidermis development, cell adhesion, and PI3K/Akt signaling pathways. Subsequently, 12 hub genes were obtained and survival analysis demonstrated SERPINE1 and SPP1 were closely related to poor prognosis of patients with HSCC and ESCC. Finally, hsa-miR-29c-3p, hsa-miR-29a-3p, and hsa-miR-29b-3p were confirmed as the top 3 interactive miRNAs that target the most hub genes according to the interaction network of miRNAs and hub genes. CONCLUSION: The common gene signatures and functional pathways identified in the study may contribute to understanding the molecular mechanisms involved in the carcinogenesis and progression of HSCC and ESCC, and provide potential diagnostic and therapeutic targets. |
format | Online Article Text |
id | pubmed-7571924 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-75719242020-10-29 Common gene signatures and key pathways in hypopharyngeal and esophageal squamous cell carcinoma: Evidence from bioinformatic analysis Zhou, Rui Liu, Denghua Zhu, Jing Zhang, Tao Medicine (Baltimore) 5700 BACKGROUND: Hypopharyngeal and esophageal squamous cell carcinoma (ESCC) are the most common double primary tumors with poor prognosis. Intensive work has been made to illuminate the etiology, but the common carcinogenic mechanism remains unclear. Thus, we conducted the study to seek to find the common gene signatures and key functional pathways associated with oncogenesis and treatment in hypopharyngeal squamous cell carcinoma (HSCC) and ESCC by bioinformatic analysis. METHODS: Three independent datasets (GSE2379, GSE20347, and GSE75241) were screened out from the Gene Expression Omnibus (GEO) database and the overlapping differentially expressed genes (DEGs) were identified using GEO2R online platform. Subsequently, the Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis of DEGs were conducted using database for annotation, visualization and integrated discovery (DAVID). Meanwhile, the protein–protein interaction network (PPI) constructed by search tool for the retrieval of interacting genes (STRING) was visualized using Cytoscape. Afterwards, the most key module and hub genes were extracted from the PPI network using the Molecular Complex Detection plugin. Moreover, the gene expression profiling interactive analysis (GEPIA) was applied to verify the expression differences and conduct the survival analyses of hub genes. Finally, the interaction network of miRNAs and hub genes constructed by encyclopedia of RNA interactomes (ENCORI) was visualized using Cytoscape. RESULTS: A total of 43 DEGs were identified, comprising 25 upregulated genes and 18 downregulated genes, which were mainly involved in the extracellular matrix-receptor interaction, collagen metabolic, epidermis development, cell adhesion, and PI3K/Akt signaling pathways. Subsequently, 12 hub genes were obtained and survival analysis demonstrated SERPINE1 and SPP1 were closely related to poor prognosis of patients with HSCC and ESCC. Finally, hsa-miR-29c-3p, hsa-miR-29a-3p, and hsa-miR-29b-3p were confirmed as the top 3 interactive miRNAs that target the most hub genes according to the interaction network of miRNAs and hub genes. CONCLUSION: The common gene signatures and functional pathways identified in the study may contribute to understanding the molecular mechanisms involved in the carcinogenesis and progression of HSCC and ESCC, and provide potential diagnostic and therapeutic targets. Lippincott Williams & Wilkins 2020-10-16 /pmc/articles/PMC7571924/ /pubmed/33080677 http://dx.doi.org/10.1097/MD.0000000000022434 Text en Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc. http://creativecommons.org/licenses/by-nc/4.0 This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc/4.0 |
spellingShingle | 5700 Zhou, Rui Liu, Denghua Zhu, Jing Zhang, Tao Common gene signatures and key pathways in hypopharyngeal and esophageal squamous cell carcinoma: Evidence from bioinformatic analysis |
title | Common gene signatures and key pathways in hypopharyngeal and esophageal squamous cell carcinoma: Evidence from bioinformatic analysis |
title_full | Common gene signatures and key pathways in hypopharyngeal and esophageal squamous cell carcinoma: Evidence from bioinformatic analysis |
title_fullStr | Common gene signatures and key pathways in hypopharyngeal and esophageal squamous cell carcinoma: Evidence from bioinformatic analysis |
title_full_unstemmed | Common gene signatures and key pathways in hypopharyngeal and esophageal squamous cell carcinoma: Evidence from bioinformatic analysis |
title_short | Common gene signatures and key pathways in hypopharyngeal and esophageal squamous cell carcinoma: Evidence from bioinformatic analysis |
title_sort | common gene signatures and key pathways in hypopharyngeal and esophageal squamous cell carcinoma: evidence from bioinformatic analysis |
topic | 5700 |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571924/ https://www.ncbi.nlm.nih.gov/pubmed/33080677 http://dx.doi.org/10.1097/MD.0000000000022434 |
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