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Functional transcriptomic annotation and protein–protein interaction network analysis identify NEK2, BIRC5, and TOP2A as potential targets in obese patients with luminal A breast cancer
PURPOSE: Although obesity is a risk factor for breast cancer, little effort has been made in the identification of druggable molecular alterations in obese–breast cancer patients. Tumors are controlled by their surrounding microenvironment, in which the adipose tissue is a main component. In this wo...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842257/ https://www.ncbi.nlm.nih.gov/pubmed/29330624 http://dx.doi.org/10.1007/s10549-017-4652-3 |
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author | Nuncia-Cantarero, Miriam Martinez-Canales, Sandra Andrés-Pretel, Fernando Santpere, Gabriel Ocaña, Alberto Galan-Moya, Eva Maria |
author_facet | Nuncia-Cantarero, Miriam Martinez-Canales, Sandra Andrés-Pretel, Fernando Santpere, Gabriel Ocaña, Alberto Galan-Moya, Eva Maria |
author_sort | Nuncia-Cantarero, Miriam |
collection | PubMed |
description | PURPOSE: Although obesity is a risk factor for breast cancer, little effort has been made in the identification of druggable molecular alterations in obese–breast cancer patients. Tumors are controlled by their surrounding microenvironment, in which the adipose tissue is a main component. In this work, we intended to describe molecular alterations at a transcriptomic and protein–protein interaction (PPI) level between obese and non-obese patients. METHODS AND RESULTS: Gene expression data of 269 primary breast tumors were compared between normal-weight (BMI < 25, n = 130) and obese (IMC > 30, n = 139) patients. No significant differences were found for the global breast cancer population. However, within the luminal A subtype, upregulation of 81 genes was observed in the obese group (FC ≥ 1.4). Next, we explored the association of these genes with patient outcome, observing that 39 were linked with detrimental outcome. Their PPI map formed highly compact cluster and functional annotation analyses showed that cell cycle, cell proliferation, cell differentiation, and cellular response to extracellular stimuli were the more altered functions. Combined analyses of genes within the described functions are correlated with poor outcome. PPI network analyses for each function were to search for druggable opportunities. We identified 16 potentially druggable candidates. Among them, NEK2, BIRC5, and TOP2A were also found to be amplified in breast cancer, suggesting that they could act as strategic players in the obese-deregulated transcriptome. CONCLUSION: In summary, our in silico analysis describes molecular alterations of luminal A tumors and proposes a druggable PPI network in obese patients with potential for translation to the clinical practice. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10549-017-4652-3) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5842257 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-58422572018-03-19 Functional transcriptomic annotation and protein–protein interaction network analysis identify NEK2, BIRC5, and TOP2A as potential targets in obese patients with luminal A breast cancer Nuncia-Cantarero, Miriam Martinez-Canales, Sandra Andrés-Pretel, Fernando Santpere, Gabriel Ocaña, Alberto Galan-Moya, Eva Maria Breast Cancer Res Treat Preclinical Study PURPOSE: Although obesity is a risk factor for breast cancer, little effort has been made in the identification of druggable molecular alterations in obese–breast cancer patients. Tumors are controlled by their surrounding microenvironment, in which the adipose tissue is a main component. In this work, we intended to describe molecular alterations at a transcriptomic and protein–protein interaction (PPI) level between obese and non-obese patients. METHODS AND RESULTS: Gene expression data of 269 primary breast tumors were compared between normal-weight (BMI < 25, n = 130) and obese (IMC > 30, n = 139) patients. No significant differences were found for the global breast cancer population. However, within the luminal A subtype, upregulation of 81 genes was observed in the obese group (FC ≥ 1.4). Next, we explored the association of these genes with patient outcome, observing that 39 were linked with detrimental outcome. Their PPI map formed highly compact cluster and functional annotation analyses showed that cell cycle, cell proliferation, cell differentiation, and cellular response to extracellular stimuli were the more altered functions. Combined analyses of genes within the described functions are correlated with poor outcome. PPI network analyses for each function were to search for druggable opportunities. We identified 16 potentially druggable candidates. Among them, NEK2, BIRC5, and TOP2A were also found to be amplified in breast cancer, suggesting that they could act as strategic players in the obese-deregulated transcriptome. CONCLUSION: In summary, our in silico analysis describes molecular alterations of luminal A tumors and proposes a druggable PPI network in obese patients with potential for translation to the clinical practice. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10549-017-4652-3) contains supplementary material, which is available to authorized users. Springer US 2018-01-12 2018 /pmc/articles/PMC5842257/ /pubmed/29330624 http://dx.doi.org/10.1007/s10549-017-4652-3 Text en © The Author(s) 2018 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. |
spellingShingle | Preclinical Study Nuncia-Cantarero, Miriam Martinez-Canales, Sandra Andrés-Pretel, Fernando Santpere, Gabriel Ocaña, Alberto Galan-Moya, Eva Maria Functional transcriptomic annotation and protein–protein interaction network analysis identify NEK2, BIRC5, and TOP2A as potential targets in obese patients with luminal A breast cancer |
title | Functional transcriptomic annotation and protein–protein interaction network analysis identify NEK2, BIRC5, and TOP2A as potential targets in obese patients with luminal A breast cancer |
title_full | Functional transcriptomic annotation and protein–protein interaction network analysis identify NEK2, BIRC5, and TOP2A as potential targets in obese patients with luminal A breast cancer |
title_fullStr | Functional transcriptomic annotation and protein–protein interaction network analysis identify NEK2, BIRC5, and TOP2A as potential targets in obese patients with luminal A breast cancer |
title_full_unstemmed | Functional transcriptomic annotation and protein–protein interaction network analysis identify NEK2, BIRC5, and TOP2A as potential targets in obese patients with luminal A breast cancer |
title_short | Functional transcriptomic annotation and protein–protein interaction network analysis identify NEK2, BIRC5, and TOP2A as potential targets in obese patients with luminal A breast cancer |
title_sort | functional transcriptomic annotation and protein–protein interaction network analysis identify nek2, birc5, and top2a as potential targets in obese patients with luminal a breast cancer |
topic | Preclinical Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842257/ https://www.ncbi.nlm.nih.gov/pubmed/29330624 http://dx.doi.org/10.1007/s10549-017-4652-3 |
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