2026-04-17T06:50:36Zhttps://recercat.cat/oai/request

oai:recercat.cat:2072/4272902026-03-13T04:34:08Zcom_2072_98col_2072_378192

00925njm 22002777a 4500 dc Hergueta-Redondo, Marta author Sarrio, David author Molina-Crespo, Ángela author Vicario, Rocío author Bernadó Morales, Cristina author Martínez, Lidia author Rojo-Sebastián, Alejandro author Serra-Musach, Jordi author Mota, Alba author Martínez-Ramírez, Ángel author Castilla, Maria Ángeles author González-Martin, Antonio author Pernas, Sonia author Cano, Amparo author Cortés Castán, Javier author Nuciforo, Paolo author Peg, Vicente author Palacios, José author Pujana, Miguel Ángel author Arribas, Joaquín V. author Moreno-Bueno, Gema author Universitat Autònoma de Barcelona author 2016 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. 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. HER2-positive breast cancer Gasdermin B Clinical behaviour Predictive biomarker Resistance to therapy Gasdermin B expression predicts poor clinical outcome in HER2-positive breast cancer