Abstract 4409
Background
Worldwide, Breast cancer (BC) is the leading cause of cancer-related mortality in women. In Argentina, breast cancer is the second leading cause of death in women, with an incidence of 18.47%. Given the importance of breast cancer for public health, and the diversity of patients’ response to current therapies, the identification of new therapeutic targets is crucial. Rac1 is a Rho GTPase widely involved in motility, mitogenesis, transformation, and metastasis. P-Rex1 is a Rac1 activator essential for the migration of breast cancer cells. It has been reported that P-Rex1 is overexpressed in breast cancer of the luminal type and that its silencing inhibits the migration of cancer cells. In order to validate P-Rex1 as a therapeutic target and/or prognostic biomarker, we aimed to analyze its presence in samples of Argentinean patients from the Marie Curie Hospital of Buenos Aires City, and determine its relationship with clinical and histopathological parameters.
Methods
The levels of P-Rex1 were determined both in biopsy material and in tumor tissue (and its corresponding healthy adjacent tissue) from primary surgery of patients not undergoing neoadjuvant therapy. The levels of messenger RNA (mRNA) were analyzed by quantitative PCR and protein by western blot (WB) and immunohistochemistry.
Results
When the mRNA levels of the biopsies classified according to the molecular subtype were compared, elevated P-Rex1 levels were observed not only in those samples classified as ER+/PR+ breast cancer but also in 50% of the samples of triple negative breast cancer (TNBC). These data were validated by an in-silico analysis made from public access databases (Metabric and the GEO repository of NCBI). P-Rex overexpression in TNBC patients has not been previously reported. The aberrant expression of P-Rex1 was detected in all stages of the disease, and a negative correlation between the expression of P-REX1 and the proliferation marker Ki-67 was determined. P-Rex1 levels were significantly higher in tumors compared to normal breast samples, in agreement with previous reports.
Conclusions
These results confirm the potential of P-Rex1 as a therapeutic target not only for the treatment of luminal tumors but also for a certain population of TNBC patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Eva Wertheimer.
Funding
Instituto Nacional del Cáncer-Ministerio de Salud-Argentina (INC, Asistencia Financiera IV, 2018).
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
4526 - Long-term outcome of neoadjuvant tyrosine kinase inhibitors (TKI) in locally advanced dermatofibrosarcoma protuberans (DFSP)
Presenter: Jessica Beaziz
Session: Poster Display session 1
Resources:
Abstract
1214 - Neo-adjuvant (NA) Imatinib for gastrointestinal stromal tumours (GISTs): What is the optimal length of treatment?
Presenter: Tom Wilson
Session: Poster Display session 1
Resources:
Abstract
2690 - Gastrointestinal Stromal Tumours (GIST) in adolescents and young adults (AYA)
Presenter: Nikki Ijzerman
Session: Poster Display session 1
Resources:
Abstract
4558 - Radiomics improves response evaluation for desmoid tumors treated with chemotherapy
Presenter: Amandine Crombe
Session: Poster Display session 1
Resources:
Abstract
2751 - Radiomics of gastrointestinal stromal tumors; risk classification based on computed tomography images – a pilot study
Presenter: Milea Timbergen
Session: Poster Display session 1
Resources:
Abstract
2737 - Differentiating well-differentiated liposarcomas from lipomas using a radiomics approach
Presenter: Melissa Vos
Session: Poster Display session 1
Resources:
Abstract
1282 - The immune landscape of chondrosarcoma reveals an anti inflammatory environment
Presenter: Iseulys Richert
Session: Poster Display session 1
Resources:
Abstract
1572 - Impact of Immunotherapy and Targeted Therapy on Tumor Growth Rate in Sarcoma
Presenter: Esmail Al-ezzi
Session: Poster Display session 1
Resources:
Abstract
3414 - DNA methylation profiles of angiosarcoma subtypes.
Presenter: Marije Weidema
Session: Poster Display session 1
Resources:
Abstract
3411 - Prognostic significance of circulating PD-1, PD-L1, pan-BTN3As and BTN3A1 in patients with metastatic gastrointestinal stromal tumors (mGISTs)
Presenter: Daniele Fanale
Session: Poster Display session 1
Resources:
Abstract