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
2433 - Boiling Histotripsy-induced Mechanical Ablation Modulates Tumour Microenvironment by Promoting Immunogenic Cell Death of Cancers
Presenter: Cheol-Hee Shin
Session: Poster Display session 1
Resources:
Abstract
2663 - The bacterial receptor NOD2 mediates LGR5+ intestinal stem cells protection against irradiation via mitophagy activation
Presenter: Antonin Levy
Session: Poster Display session 1
Resources:
Abstract
3213 - Pulse mode irradiation regimen of PDT results in high progression free and overall survival in mice with model tumor
Presenter: Alexey Bogdanov
Session: Poster Display session 1
Resources:
Abstract
3722 - Proton-sensitizing effect of small molecule inhibitor of P300 histone acetyltransferase C646 in human pancreatic cancer cells.
Presenter: Sungwon Shin
Session: Poster Display session 1
Resources:
Abstract
5805 - Red-Blood-Cell-Membrane-Enveloped Magnetic Nanoclusters as a Biomimetic Theranostic Nanoplatform for Bimodal Imaging Guided Cancer Photothermal Therapy
Presenter: sheng wang
Session: Poster Display session 1
Resources:
Abstract
5251 - Urine cell-free and extracellular vesicle cargo miRNAs as biomarkers for prostate cancer diagnosis
Presenter: Ivan Zaporozhchenko
Session: Poster Display session 1
Resources:
Abstract
3657 - Parkin, APEX1 and BCL2L1 Tissue Expression in Southern Brazilian Patients with Different Breast Cancer Molecular Subtypes
Presenter: Bianca Cabral
Session: Poster Display session 1
Resources:
Abstract
2839 - Obesity and prognosis in breast cancer
Presenter: Noha Ibrahim
Session: Poster Display session 1
Resources:
Abstract
5132 - SIPA1 is a modulator of HGF induced tumor metastasis via the regulation of tight junctions in lung adenocarcinoma cells
Presenter: Chang Liu
Session: Poster Display session 1
Resources:
Abstract
860 - Dose differential modulation of the autophagic behavior of estrogen expressing breast carcinoma cells
Presenter: Mariam Fouad
Session: Poster Display session 1
Resources:
Abstract