Differential expression of neurogenes among breast cancer subtypes identifies high risk patients
Fernández-Nogueira, Patricia (Universitat de Barcelona. Departament de Medicina)
Bragado, Paloma (Hospital Clínic i Provincial de Barcelona)
Almendro, Vanessa (Brigham and Women's Hospital (Boston, Estats Units d'Amèrica))
Ametller, Elisabet (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Rios, Jose (Universitat Autònoma de Barcelona. Departament de Medicina)
Choudhury, Sibgat (Brigham and Women's Hospital (Boston, Estats Units d'Amèrica))
Mancino, Mario (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Gascón, Pedro (Universitat de Barcelona. Departament de Medicina)
Data: |
2015 |
Resum: |
The nervous system is now recognized to be a relevant component of the tumor microenvironment. Receptors for neuropeptides and neurotransmitters have been identified in breast cancer. However, very little is known about the role of neurogenes in regulating breast cancer progression. Our purpose was to identify neurogenes associated with breast cancer tumorigenesis with a potential to be used as biomarker and/or targets for treatment. We used three databases of human genes: GeneGo, GeneCards and Eugenes to generate a list of 1266 relevant neurogenes. Then we used bioinformatics tools to interrogate two published breast cancer databases SAGE and MicMa (n =96) and generated a list of 7 neurogenes that are differentially express among breast cancer subtypes. The clinical potential was further investigated using the GOBO database (n =1881). We identified 6 neurogenes that are differentially expressed among breast cancer subtypes and whose expression correlates with prognosis. Histamine receptor1 (HRH1), neuropilin2 (NRP2), ephrin-B1 (EFNB1), neural growth factor receptor (NGFR) and amyloid precursor protein (APP) were differentially overexpressed in basal and HER2-enriched tumor samples and syntaxin 1A (STX1A) was overexpressed in HER2-enriched and luminal B tumors. Analysis of HRH1, NRP2, and STX1A expression using the GOBO database showed that their expression significantly correlated with a shorter overall survival (p < 0. 0001) and distant metastasis-free survival (p < 0. 0001). In contrast, elevated co-expression of NGFR, EFNB1 and APP was associated with longer overall (p < 0. 0001) and metastasis-free survival (p < 0. 0001). We propose that HRH1, NRP2, and STX1A can be used as prognostic biomarkers and therapeutic targets for basal and HER2-enriched breast cancer subtypes. |
Ajuts: |
Instituto de Salud Carlos III PI12-01706 Instituto de Salud Carlos III RD12-00360055
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Drets: |
Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. ![Creative Commons](/img/licenses/by.ico) |
Llengua: |
Anglès |
Document: |
Article ; recerca ; Versió publicada |
Matèria: |
Breast cancer ;
Neurogenes ;
Neuropeptides ;
Neurotransmitters ;
Tumor microenvironment |
Publicat a: |
Oncotarget, Vol. 7 (december 2015) , p. 5313-5326, ISSN 1949-2553 |
DOI: 10.18632/oncotarget.6543
PMID: 26673618
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