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Title

Gasdermin B expression predicts poor clinical outcome in HER2-positive breast cancer

AuthorsHergueta-Redondo, Marta; Sarrió, David ; Molina-Crespo, Ángela; Martínez, Lidia; Mota, Alba; Castilla, María Ángeles; Cano, Amparo ; Palacios, José; Pujana, Miguel Ángel; Moreno-Bueno, Gema
KeywordsResistance to therapy
HER2-positive breast cancer
Gasdermin B
Clinical behaviour
Predictive biomarker
Issue Date2016
PublisherImpact Journals
CitationOncotarget 7(35): 56295-56308 (2016)
AbstractAround, 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.
DescriptionThis is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.
Publisher version (URL)https://doi.org/10.18632/oncotarget.10787
URIhttp://hdl.handle.net/10261/151074
DOI10.18632/oncotarget.10787
Identifiersdoi: 10.18632/oncotarget.10787
e-issn: 1949-2553
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