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Study on the Selection of the Targets of Esophageal Carcinoma and Interventions of Ginsenosides Based on Network Pharmacology and Bioinformatics

BACKGROUND: Esophageal carcinoma (ESCA) is not only a threat to people's health but also the sixth most common cause of cancer-related mortality worldwide. METHODS: In this study, the key targets of ESCA are screened through GeneCards and DisGeNET databases combined with the Gene Expression Omn...

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Autores principales: Yang, Xin, Li, Yahui, Qian, Haibing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333027/
https://www.ncbi.nlm.nih.gov/pubmed/32714406
http://dx.doi.org/10.1155/2020/4821056
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author Yang, Xin
Li, Yahui
Qian, Haibing
author_facet Yang, Xin
Li, Yahui
Qian, Haibing
author_sort Yang, Xin
collection PubMed
description BACKGROUND: Esophageal carcinoma (ESCA) is not only a threat to people's health but also the sixth most common cause of cancer-related mortality worldwide. METHODS: In this study, the key targets of ESCA are screened through GeneCards and DisGeNET databases combined with the Gene Expression Omnibus (GEO) database (GSE1420 and GSE20347). Then, data associated with ESCA samples are downloaded from The Cancer Genome Atlas (TCGA) database for integrated analysis. Moreover, the effect of epithelial cell adhesion molecule (EpCAM) expression on the survival of patients with ESCA is evaluated by Kaplan–Meier and Cox analyses. The virtual screening is carried out using a Suflex-Dock molecular docking module. The chemical components, which have been well bound to EpCAM, are screened out based on a total score >5 as a threshold. Ginsenosides and EpCAM are analyzed by LigPlot + v.2.2 software to identify the binding sites. RESULTS: Four ESCA targets are obtained from GeneCards, DisGeNET, and GEO databases. In this study, it is found that high EpCAM expression is associated with histologic grade, stage, patient age, N classification, T classification, and radiation therapy. The Kaplan–Meier curves for overall survival also show that the higher expression of EpCAM is associated with worse outcomes in patients with ESCA. Univariate and multivariate Cox analyses indicate that EpCAM mRNA expression might be a useful biomarker for ESCA(P < 0.05). Molecular docking technology suggests that ginsenoside Rg3 and ginsenoside Rh2 can easily establish good docking modes and have a high affinity with EpCAM. The 6′-hydroxyl and 6″-hydroxyl on the 3-glycosyl of ginsenoside Rg3 are prone to form hydrogen bonds (Lys151 and Lys221) with the active sites of EpCAM ligand binding domain. The hydroxyl groups on the 12 sites of the ginsenoside Rh2 glycoside framework are found to have hydrogen bonding with Leu240. The formation of hydrogen bonds plays an important role in binding of ginsenoside Rg3 and ginsenoside Rh2 to EpCAM, as well as the stability of EpCAM conformation. CONCLUSION: EpCAM may be determined as a potential biomarker for early diagnosis and prognosis of ESCA. Ginsenoside Rg3 and ginsenoside Rh2 have potential antiesophageal cancer activities. This experiment provides a reference for the study of the chemical compositions of ginsenosides in the treatment of esophageal cancer.
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spelling pubmed-73330272020-07-24 Study on the Selection of the Targets of Esophageal Carcinoma and Interventions of Ginsenosides Based on Network Pharmacology and Bioinformatics Yang, Xin Li, Yahui Qian, Haibing Evid Based Complement Alternat Med Research Article BACKGROUND: Esophageal carcinoma (ESCA) is not only a threat to people's health but also the sixth most common cause of cancer-related mortality worldwide. METHODS: In this study, the key targets of ESCA are screened through GeneCards and DisGeNET databases combined with the Gene Expression Omnibus (GEO) database (GSE1420 and GSE20347). Then, data associated with ESCA samples are downloaded from The Cancer Genome Atlas (TCGA) database for integrated analysis. Moreover, the effect of epithelial cell adhesion molecule (EpCAM) expression on the survival of patients with ESCA is evaluated by Kaplan–Meier and Cox analyses. The virtual screening is carried out using a Suflex-Dock molecular docking module. The chemical components, which have been well bound to EpCAM, are screened out based on a total score >5 as a threshold. Ginsenosides and EpCAM are analyzed by LigPlot + v.2.2 software to identify the binding sites. RESULTS: Four ESCA targets are obtained from GeneCards, DisGeNET, and GEO databases. In this study, it is found that high EpCAM expression is associated with histologic grade, stage, patient age, N classification, T classification, and radiation therapy. The Kaplan–Meier curves for overall survival also show that the higher expression of EpCAM is associated with worse outcomes in patients with ESCA. Univariate and multivariate Cox analyses indicate that EpCAM mRNA expression might be a useful biomarker for ESCA(P < 0.05). Molecular docking technology suggests that ginsenoside Rg3 and ginsenoside Rh2 can easily establish good docking modes and have a high affinity with EpCAM. The 6′-hydroxyl and 6″-hydroxyl on the 3-glycosyl of ginsenoside Rg3 are prone to form hydrogen bonds (Lys151 and Lys221) with the active sites of EpCAM ligand binding domain. The hydroxyl groups on the 12 sites of the ginsenoside Rh2 glycoside framework are found to have hydrogen bonding with Leu240. The formation of hydrogen bonds plays an important role in binding of ginsenoside Rg3 and ginsenoside Rh2 to EpCAM, as well as the stability of EpCAM conformation. CONCLUSION: EpCAM may be determined as a potential biomarker for early diagnosis and prognosis of ESCA. Ginsenoside Rg3 and ginsenoside Rh2 have potential antiesophageal cancer activities. This experiment provides a reference for the study of the chemical compositions of ginsenosides in the treatment of esophageal cancer. Hindawi 2020-06-24 /pmc/articles/PMC7333027/ /pubmed/32714406 http://dx.doi.org/10.1155/2020/4821056 Text en Copyright © 2020 Xin Yang et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Yang, Xin
Li, Yahui
Qian, Haibing
Study on the Selection of the Targets of Esophageal Carcinoma and Interventions of Ginsenosides Based on Network Pharmacology and Bioinformatics
title Study on the Selection of the Targets of Esophageal Carcinoma and Interventions of Ginsenosides Based on Network Pharmacology and Bioinformatics
title_full Study on the Selection of the Targets of Esophageal Carcinoma and Interventions of Ginsenosides Based on Network Pharmacology and Bioinformatics
title_fullStr Study on the Selection of the Targets of Esophageal Carcinoma and Interventions of Ginsenosides Based on Network Pharmacology and Bioinformatics
title_full_unstemmed Study on the Selection of the Targets of Esophageal Carcinoma and Interventions of Ginsenosides Based on Network Pharmacology and Bioinformatics
title_short Study on the Selection of the Targets of Esophageal Carcinoma and Interventions of Ginsenosides Based on Network Pharmacology and Bioinformatics
title_sort study on the selection of the targets of esophageal carcinoma and interventions of ginsenosides based on network pharmacology and bioinformatics
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333027/
https://www.ncbi.nlm.nih.gov/pubmed/32714406
http://dx.doi.org/10.1155/2020/4821056
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