Avaliação da atividade das enzimas NTPDase 1 (CD39) e Ecto-5'Nucleotidase (CD73) no plasma de pacientes idosas com câncer de mama

Abstract

Breast cancer (BC) is the most common type of cancer and the biggest mortality cause among women in whole world, being strongly associated to ageing. This has a huge importance, once rise of population’s life expectancy is directly related to cancer (re) appearance risk. However, elderly population is frequently excluded from clinical trials and its treatments are based in data obtained from trials with younger population, not being ideal. This cancer’s etiology is multifactorial, evolving endocrine, reproductive and environmental factors and, less frequently, familiar predisposition. Tumor severity is defined by its size, node commitment, presence of metastasis, hormone receptors (estrogen and progesterone) and human epidermal growth factor receptor (HER2) expression, and the absence of all receptors, characterizing the most serious subtype. This study aimed to analyze the tumor’s molecular features on elderly patients, evaluating nucleotide hydrolysis (ATP to ADP and ADP to AMP made by CD39 and AMP to adenosine by CD73) in plasma blood as possible prognostic biomarkers and/or therapeutic targets, in order to improve these patients’ disease outcomes. Peripheral blood samples were collected from 24 BC patients with age above 60 years old at the moment of diagnosis and after 6 months of treatment, and from 15 elderly patients without cancer diagnosis. The nucleotide hydrolysis analysis of the samples from BC patients at diagnosis were related to control, prognostic factors, like Ki67, known as proliferation rate marker and the samples from the same patients after 6 months of treatment. The mean age of patients were 68 years old and about 66,6% with tumors stage I and II, and 33,3% staging III and IV, representing worse prognosis. Results showed BC patients had lower ADP and higher AMP hydrolysis when compared to control. When analyzing differences between the diagnose samples and the ones collected after 6 months, we were able to show a significant reduction on AMPase activity, making the profile of treated individuals look like the healthy individuals’, independently of which treatment was used. When comparing the hydrolysis rate with Ki67 results, where 47% of the patients presented low rate (< 20%), there was a tendency of these ones present lower AMP hydrolysis. This way, we can conclude that understanding the ectonucleotidases activity role in cancer progression can help this disease complexity understanding, looking forward to improve early detection and therapeutic approach on elderly patients.