RT Journal Article
T1 Gasdermin B expression predicts poor clinical outcome in HER2-positive breast cancer
A1 Hergueta-Redondo, Marta
A1 Sarrio, David
A1 Molina-Crespo, Angela
A1 Vicario, Rocio
A1 Bernado-Morales, Cristina
A1 Martinez, Lidia
A1 Rojo-Sebastian, Alejandro
A1 Serra-Musach, Jordi
A1 Mota, Alba
A1 Martinez-Ramirez, Angel
A1 Angeles Castilla, Ma
A1 Gonzalez-Martin, Antonio
A1 Pernas, Sonia
A1 Cano, Amparo
A1 Cortes, Javier
A1 Nuciforo, Paolo G.
A1 Peg, Vicente
A1 Palacios, Jose
A1 Angel Pujana, Miguel
A1 Arribas, Joaquin
A1 Moreno-Bueno, Gema
K1 HER2-positive breast cancer
K1 gasdermin B
K1 clinical behaviour
K1 predictive biomarker
K1 resistance to therapy
K1 Her2 amplicon includes
K1 Adjuvant chemotherapy
K1 Trastuzumab emtansine
K1 Survival
K1 Growth
K1 Receptor
K1 Gsdml
K1 Lapatinib
K1 Therapy
K1 Plus
AB 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.
PB Impact journals llc
YR 2016
FD 2016-08-30
LK http://hdl.handle.net/10668/19435
UL http://hdl.handle.net/10668/19435
LA en
DS RISalud
RD Apr 11, 2025