Please use this identifier to cite or link to this item: https://hdl.handle.net/20.500.12530/25746
Title: Gasdermin B expression predicts poor clinical outcome in HER2-positive breast cancer.
Authors: 
Keywords: 
Mesh: 
Issue Date: 30-Aug-2016
Citation: Oncotarget.2016 Aug;(7)35:56295-56308
Abstract: 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.
PMID: 27462779
URI: https://hdl.handle.net/20.500.12530/25746
Rights: openAccess
Appears in Collections:Fundaciones e Institutos de Investigación > IIS H. U. La Paz > Artículos
Fundaciones e Institutos de Investigación > IIS H. U. Ramón y Cajal > Artículos

Files in This Item:
File Description SizeFormat 
PMC5302915.pdf7.04 MBAdobe PDFThumbnail
View/Open


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.