Produtos de glicação avançada no plasma de mulheres com diagnóstico recente de câncer de mama em diferentes estágios e classificação molecular da doença

Abstract

Advanced glycation products (AGE) are prevalent in several conditions associated with the genesis of breast cancer, and in the tumor microenvironment, favoring oxidative and inflammatory insult and disturbing lipid homeostasis. AGE is recognized by the receptor for AGE, AGER, which mediates signaling pathways associated with increased proliferative and invasive capacity of breast tumors. Soluble forms of AGER (sAGER) inhibit AGE signaling and are indicated as negative modulators of the chronic complications mediated by AGE. The objective of the present study was to evaluate in newly diagnosed women with invasive breast cancer: a) the association between the plasma concentration of AGE and isoforms of soluble AGER, with the prognosis of the disease according to its molecular classification and clinical stage. Female subjects, between 18 and 80 years of AGE, with a recent diagnosis of breast cancer, virgins of treatment, with molecular classification and clinical prognostic staging of tumor I to IV. Healthy women matched for AGE and body mass index were included as a control group. Concentrations of plasma AGE and pentosidine were determined by fluorimetry. sAGER was measured by ELISA, and glyoxalase 1 will be evaluated by enzymatic colorimetric method. The frequency of molecular types of breast cancer was luminal B (38.3%), luminal A (29%), HER2 (16.9%), and TN (15.8%). The initial stages of the disease (I and II) represented 69% and the advanced ones (stages III and IV), 31% of the sample. Plasma lipid profile and lipid ratios were similar between the control and breast cancer groups. The plasma concentration of total AGE was similar between the control and breast cancer groups, but it was lower in the advanced stages of the disease (III and IV) compared to the initial stages (I and II). Plasma pentosidine was similar between groups and between molecular types and stages of breast cancer but was lower in the advanced stages of the disease (III and IV) compared to the initial stage (I). The concentration of sAGER was similar between breast cancer and control group, molecular types, and clinical stages of the disease. The findings demonstrate a reduction in plasma concentrations of AGE in the advanced stages of breast cancer. More studies are needed to validate the use of AGE as biomarkers or mediators of breast cancer and to establish their clinical relevance 10 and usefulness in prognosis, in guiding therapeutic decisions and clinical follow-up.