Prognostic and predictive value of Pleckstrin homology-like domain, family A family members in breast cancer

Author:

R Mangone Flavia12ORCID,AV Valoyes Maira12,G do Nascimento Renan12,PF Conceição Mércia12,R Bastos Daniel12,C Pavanelli Ana12,C Soares Iberê3,S de Mello Evandro3,Nonogaki Suely4,AB de T Osório Cynthia4,A Nagai Maria12ORCID

Affiliation:

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.

Funder

Fundação de Amparo à Pesquisa do Estado de São Paulo

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Publisher

Future Medicine Ltd

Subject

Biochemistry (medical),Clinical Biochemistry,Drug Discovery

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