Web of Science: 31 cites, Scopus: 34 cites, Google Scholar: cites,
Gasdermin B expression predicts poor clinical outcome in HER2-positive breast cancer
Hergueta-Redondo, Marta (Universidad Autónoma de Madrid. Instituto de Investigaciones Biomédicas "Alberto Sols")
Sarrio, David (Universidad Autónoma de Madrid. Instituto de Investigaciones Biomédicas "Alberto Sols")
Molina-Crespo, Ángela (Universidad Autónoma de Madrid. Instituto de Investigaciones Biomédicas "Alberto Sols")
Vicario, Rocío (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Bernadó Morales, Cristina (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Martínez, Lidia (Universidad Autónoma de Madrid. Instituto de Investigaciones Biomédicas "Alberto Sols")
Rojo-Sebastián, Alejandro (Pathology Department, MD Anderson Cancer Center, Madrid, Spain)
Serra-Musach, Jordi (Institut d'Investigació Biomèdica de Bellvitge)
Mota, Alba (Translational Research Laboratory, MD Anderson Internacional Foundation, Madrid, Spain)
Martínez-Ramírez, Ángel (Cytogenetics Department, MD Anderson Cancer Center, Madrid, Spain)
Castilla, Maria Ángeles (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
González-Martin, Antonio (Oncology Department, MD Anderson Cancer Center, Madrid, Spain)
Pernas, Sonia (Institut d'Investigació Biomèdica de Bellvitge)
Cano, Amparo (Universidad Autónoma de Madrid. Instituto de Investigaciones Biomédicas "Alberto Sols")
Cortes, Javier (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Nuciforo, Paolo. (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Peg, Vicente (Hospital Universitari Vall d'Hebron)
Palacios, José (Hospital Universitario Ramón y Cajal (Madrid))
Pujana, Miguel Ángel (Institut d'Investigació Biomèdica de Bellvitge)
Arribas, Joaquín (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Moreno-Bueno, Gema (Translational Research Laboratory, MD Anderson Internacional Foundation, Madrid, Spain)
Universitat Autònoma de Barcelona

Data: 2016
Resum: Around, 30-40% of HER2-positive breast cancers do not show substantial clinical benefit from the targeted therapy and, thus, the mechanisms underlying resistance remain partially unknown. Interestingly, ERBB2 is frequently co-amplified and co-expressed with neighbour genes that may play a relevant role in this cancer subtype. Here, using an in silico analysis of data from 2,096 breast tumours, we reveal a significant correlation between Gasdermin B (GSDMB) gene (located 175 kilo bases distal from ERBB2) expression and the pathological and clinical parameters of poor prognosis in HER2-positive breast cancer. Next, the analysis of three independent cohorts (totalizing 286 tumours) showed that approximately 65% of the HER2-positive cases have GSDMB gene amplification and protein over-expression. Moreover, GSDMB expression was also linked to poor therapeutic responses in terms of lower relapse free survival and pathologic complete response as well as positive lymph node status and the development of distant metastasis under neoadjuvant and adjuvant treatment settings, respectively. Importantly, GSDMB expression promotes survival to trastuzumab in different HER2-positive breast carcinoma cells, and is associated with trastuzumab resistance phenotype in vivo in Patient Derived Xenografts. In summary, our data identifies the ERBB2 co-amplified and co-expressed gene GSDMB as a critical determinant of poor prognosis and therapeutic response in HER2-positive breast cancer.
Ajuts: Instituto de Salud Carlos III PI13-00132
Instituto de Salud Carlos III RETICC RD12-0036-0007
Instituto de Salud Carlos III PI15-00854
Instituto de Salud Carlos III RETICC RD12-0036-0008
Instituto de Salud Carlos III RD12-0036-0057
Instituto de Salud Carlos III RD12-0036-0064
Agència de Gestió d'Ajuts Universitaris i de Recerca 2014-SGR-364
Nota: Altres ajuts: This work has been supported by the Community of Madrid (grant S2010/BMD-2303 to GMB), the Breast Cancer Research Foundation (BCRF) to JA. Alba Mota is a predoctoral student supported by a FPU fellowship (Spanish Ministry of Education, Culture and Sport). David Sarrio is a postdoctoral researcher funded by the AECC Scientific Foundation.
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
Llengua: Anglès
Document: Article ; recerca ; Versió publicada
Matèria: HER2-positive breast cancer ; Gasdermin B ; Clinical behaviour ; Predictive biomarker ; Resistance to therapy
Publicat a: Oncotarget, Vol. 7 (july 2016) , p. 56295-56308, ISSN 1949-2553

DOI: 10.18632/oncotarget.10787
PMID: 27462779


14 p, 6.9 MB

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