Flavia R Mangone1,2, Maira Av Valoyes1,2, Renan G do Nascimento1,2, Mércia Pf Conceição1,2, Daniel R Bastos1,2, Ana C Pavanelli1,2, Iberê C Soares3, Evandro S de Mello3, Suely Nonogaki4, Cynthia Ab de T Osório4, Maria A Nagai1,2. 1. Discipline of Oncology, Department of Radiology & Oncology, Faculty of Medicine, University of Sao Paulo, 01246-903, Sao Paulo, Brazil. 2. Laboratory of Molecular Genetics, Center for Translational Research in Oncology, Cancer Institute of Sao Paulo, 01246-000, Sao Paulo, Brazil. 3. Department of Pathology, Instituto do Cancer, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, 01246-903, São Paulo, Brazil. 4. Department of Pathological Anatomy, A. C. Camargo Cancer Center, 01509-020, Sao Paulo, Brazil.
Abstract
Aim: The PHLDA (pleckstrin homology like domain, family A) gene family encodes proteins capable of inhibiting AKT (serine/threonine kinase) signaling through phosphoinositol binding competition. Results & methodology: Using in silico analysis, we found that Luminal A and B patients' short relapse-free survival was associated with low PHLDA1 or PHLDA3 and high PHLDA2 expression. In a cohort of 393 patients with luminal breast cancer evaluated by immunohistochemistry on tissue microarrays, we found a direct association of PHLDA3 expression with hormonal therapy response (p = 0.013). Conclusion: Our findings provide new information on the role played by the PHLDA family members as prognostic markers in breast cancer, and more importantly, we provide evidence that they might also predict a response to endocrine therapy.
Aim: The PHLDA (pleckstrin homology like domain, family A) gene family encodes proteins capable of inhibiting AKT (serine/threonine kinase) signaling through phosphoinositol binding competition. Results & methodology: Using in silico analysis, we found that Luminal A and B patients' short relapse-free survival was associated with low PHLDA1 or PHLDA3 and high PHLDA2 expression. In a cohort of 393 patients with luminal breast cancer evaluated by immunohistochemistry on tissue microarrays, we found a direct association of PHLDA3 expression with hormonal therapy response (p = 0.013). Conclusion: Our findings provide new information on the role played by the PHLDA family members as prognostic markers in breast cancer, and more importantly, we provide evidence that they might also predict a response to endocrine therapy.
Entities:
Keywords:
PHLDA; breast cancer; endocrine therapy; expression; luminal subtype
Authors: Renan Gomes do Nascimento; Jéssica de Moraes; Danilo de Oliveira Cerqueira; Sandro Jorge Januário Journal: Eur J Breast Health Date: 2022-07-01