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A Systems Biology Approach Provides Deeper Insights into Differentially Expressed Genes in Taxane-Anthracycline Chemoresistant and Non-Resistant Breast Cancers

OBJECTIVE: To date, numerous studies have been conducted to search for reasons for chemoresistance and differences in survival rates of patients receiving chemotherapy. We have sought to identify differentially expressed genes (DEGs) between predicted chemotherapy resistance and sensitive phenotypes...

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Autores principales: Sarhadi, Shamim, Sadeghi, Somayeh, Nikmanesh, Fatemeh, Soltanahmadi, Younes Pilehvar, Shahabi, Arman, Aval, Sedigheh Fekri, Zarghami, Nosratollah
Formato: Online Artículo Texto
Lenguaje:English
Publicado: West Asia Organization for Cancer Prevention 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5747381/
https://www.ncbi.nlm.nih.gov/pubmed/29072056
http://dx.doi.org/10.22034/APJCP.2017.18.10.2629
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author Sarhadi, Shamim
Sadeghi, Somayeh
Nikmanesh, Fatemeh
Soltanahmadi, Younes Pilehvar
Shahabi, Arman
Aval, Sedigheh Fekri
Zarghami, Nosratollah
author_facet Sarhadi, Shamim
Sadeghi, Somayeh
Nikmanesh, Fatemeh
Soltanahmadi, Younes Pilehvar
Shahabi, Arman
Aval, Sedigheh Fekri
Zarghami, Nosratollah
author_sort Sarhadi, Shamim
collection PubMed
description OBJECTIVE: To date, numerous studies have been conducted to search for reasons for chemoresistance and differences in survival rates of patients receiving chemotherapy. We have sought to identify differentially expressed genes (DEGs) between predicted chemotherapy resistance and sensitive phenotypes by a network as well as gene enrichment approach. METHODS: Functional modules were explored with network analysis of DEGs in predicted neoadjuvant taxane-anthracycline resistance versus sensitive cases in the GSE25066 dataset, including 508 samples. A linear model was created by limma package in R to establish DEGs. RESULTS: A gene set related to phagocytic vesicle membrane was found to be up-regulated in chemoresistance samples. Also, we found GO_CYTOKINE_ACTIVITY and GO_GROWTH_FACTOR BINDING to be up-regulated gene sets with the chemoresistance phenotype. Growth factors and cytokines are two groups of agents that induce the immune system to recruit APCs and promote tolerogenic phagocytosis. Some hub nodes like S100A8 were found to be important in the chemoresistant tumor cell network with associated high rank genes in GSEA. CONCLUSIONS: Functional gene sets and hub nodes could be considered as potential treatment targets. Moreover, by screening and enrichment analysis of a chemoresistance network, ligands and chemical agents have been found that could modify significant gene sets like the phagocytic vesicle membrane functional gene set as a key to chemoresistance. They could also impact on down- or up-regulated hub nodes.
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spelling pubmed-57473812018-02-21 A Systems Biology Approach Provides Deeper Insights into Differentially Expressed Genes in Taxane-Anthracycline Chemoresistant and Non-Resistant Breast Cancers Sarhadi, Shamim Sadeghi, Somayeh Nikmanesh, Fatemeh Soltanahmadi, Younes Pilehvar Shahabi, Arman Aval, Sedigheh Fekri Zarghami, Nosratollah Asian Pac J Cancer Prev Research Article OBJECTIVE: To date, numerous studies have been conducted to search for reasons for chemoresistance and differences in survival rates of patients receiving chemotherapy. We have sought to identify differentially expressed genes (DEGs) between predicted chemotherapy resistance and sensitive phenotypes by a network as well as gene enrichment approach. METHODS: Functional modules were explored with network analysis of DEGs in predicted neoadjuvant taxane-anthracycline resistance versus sensitive cases in the GSE25066 dataset, including 508 samples. A linear model was created by limma package in R to establish DEGs. RESULTS: A gene set related to phagocytic vesicle membrane was found to be up-regulated in chemoresistance samples. Also, we found GO_CYTOKINE_ACTIVITY and GO_GROWTH_FACTOR BINDING to be up-regulated gene sets with the chemoresistance phenotype. Growth factors and cytokines are two groups of agents that induce the immune system to recruit APCs and promote tolerogenic phagocytosis. Some hub nodes like S100A8 were found to be important in the chemoresistant tumor cell network with associated high rank genes in GSEA. CONCLUSIONS: Functional gene sets and hub nodes could be considered as potential treatment targets. Moreover, by screening and enrichment analysis of a chemoresistance network, ligands and chemical agents have been found that could modify significant gene sets like the phagocytic vesicle membrane functional gene set as a key to chemoresistance. They could also impact on down- or up-regulated hub nodes. West Asia Organization for Cancer Prevention 2017 /pmc/articles/PMC5747381/ /pubmed/29072056 http://dx.doi.org/10.22034/APJCP.2017.18.10.2629 Text en Copyright: © Asian Pacific Journal of Cancer Prevention http://creativecommons.org/licenses/BY-SA/4.0 This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License
spellingShingle Research Article
Sarhadi, Shamim
Sadeghi, Somayeh
Nikmanesh, Fatemeh
Soltanahmadi, Younes Pilehvar
Shahabi, Arman
Aval, Sedigheh Fekri
Zarghami, Nosratollah
A Systems Biology Approach Provides Deeper Insights into Differentially Expressed Genes in Taxane-Anthracycline Chemoresistant and Non-Resistant Breast Cancers
title A Systems Biology Approach Provides Deeper Insights into Differentially Expressed Genes in Taxane-Anthracycline Chemoresistant and Non-Resistant Breast Cancers
title_full A Systems Biology Approach Provides Deeper Insights into Differentially Expressed Genes in Taxane-Anthracycline Chemoresistant and Non-Resistant Breast Cancers
title_fullStr A Systems Biology Approach Provides Deeper Insights into Differentially Expressed Genes in Taxane-Anthracycline Chemoresistant and Non-Resistant Breast Cancers
title_full_unstemmed A Systems Biology Approach Provides Deeper Insights into Differentially Expressed Genes in Taxane-Anthracycline Chemoresistant and Non-Resistant Breast Cancers
title_short A Systems Biology Approach Provides Deeper Insights into Differentially Expressed Genes in Taxane-Anthracycline Chemoresistant and Non-Resistant Breast Cancers
title_sort systems biology approach provides deeper insights into differentially expressed genes in taxane-anthracycline chemoresistant and non-resistant breast cancers
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5747381/
https://www.ncbi.nlm.nih.gov/pubmed/29072056
http://dx.doi.org/10.22034/APJCP.2017.18.10.2629
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