Avaliação do receptor purinérgico P2X7 e da CD73 como biomarcadores em pacientes idosas com câncer de mama

Abstract

Breast cancer is the most prevalent neoplasm in women worldwide. Elderly women are frequently excluded from clinical studies, with a deficit in the collection of prospective data for this age group and, consequently, they are evaluated and treated according to the studies and guidelines evaluated in young women. In recent years, the focus for new types of breast cancer diagnosis and treatment has been on purinergic signaling and its role in tumor promotion and progression. The tumor microenvironment is rich in ATP production and release, which after a series of steps acts on the P2X and P2Y purinergic receptors, mediating various biological functions in the tumor, such as cell proliferation, migration, differentiation, and cell death. Therefore, the aim of this study was to evaluate the expression of the ionotropic receptor P2X7 and CD73 in biopsies of elderly patients with breast cancer and to relate them as possible prognostic biomarkers and/or therapeutic targets, in order to improve disease outcomes in this group of patients. Samples were collected from 22 elderly patients (> 60 years), assisted by the Unified Health System at the Oncology Service of Hospital São Lucas da PUCRS at the time of diagnosis, and from 12 elderly patients without a diagnosis of cancer (control group). The most expressive cancer subtype in the sample was HER2+ in 7 women (31.8%), followed by luminal B (27.3%), luminal A (22.7%) and triple negative (18.2%). The TNM system was used to classify cancer staging, where 15 elderly women (68.2%) had Clinical Stage I and II and 7 (31.8%) had Clinical Stage III and IV, representing the highest level of severity. of the disease. The evaluation of P2X7 and CD73 expression was performed using the immunohistochemical technique and was analyzed by a professional pathologist. Regarding P2X7, women aged 60 to 69 years and ≥ 70 years represented the highest number in the mildly expressed tumor grade (grade 1) 53.3% and 57.1% respectively. In the CD73 analysis, women aged 60 to 69 years maintained the representation of the highest number in the mildly expressed tumor grade (60%), but women aged ≥ 70 years had a higher incidence in the highly expressed category (grade 3), with 42, 8% of them. The expression of markers in the blood of elderly patients with breast cancer was also evaluated and compared with control patients, but there was no statistically significant difference. Data extracted from the TCGA showed that elderly women with stage T2 breast cancer had higher expression of CD73. Therefore, the need for research on the purinergic system, particularly the P2X7 and CD73 proteins, and breast cancer in elderly women is evident.