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 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:168 |
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| Enthalten in: |
Breast cancer research and treatment - 168(2018), 3 vom: 13. Apr., Seite 613-623 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Nuncia-Cantarero, Miriam [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 27.02.2019 Date Revised 14.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s10549-017-4652-3 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM279929277 |
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| 100 | 1 | |a Nuncia-Cantarero, Miriam |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a 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 |
| 264 | 1 | |c 2018 | |
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| 500 | |a Date Revised 14.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Breast cancer | |
| 650 | 4 | |a Clinical outcome | |
| 650 | 4 | |a Novel druggable targets | |
| 650 | 4 | |a Protein–protein interaction | |
| 650 | 4 | |a Targeted therapy | |
| 650 | 4 | |a Transcriptomic analysis | |
| 650 | 7 | |a BIRC5 protein, human |2 NLM | |
| 650 | 7 | |a Poly-ADP-Ribose Binding Proteins |2 NLM | |
| 650 | 7 | |a Survivin |2 NLM | |
| 650 | 7 | |a NEK2 protein, human |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a NIMA-Related Kinases |2 NLM | |
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| 650 | 7 | |a DNA Topoisomerases, Type II |2 NLM | |
| 650 | 7 | |a EC 5.99.1.3 |2 NLM | |
| 650 | 7 | |a TOP2A protein, human |2 NLM | |
| 650 | 7 | |a EC 5.99.1.3 |2 NLM | |
| 700 | 1 | |a Martinez-Canales, Sandra |e verfasserin |4 aut | |
| 700 | 1 | |a Andrés-Pretel, Fernando |e verfasserin |4 aut | |
| 700 | 1 | |a Santpere, Gabriel |e verfasserin |4 aut | |
| 700 | 1 | |a Ocaña, Alberto |e verfasserin |4 aut | |
| 700 | 1 | |a Galan-Moya, Eva Maria |e verfasserin |4 aut | |
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