Investigação dos mecanismos moleculares associados à adesão celular, inflamação e crescimento tumoral através da expressão proteica e gênica

Abstract

Introduction: Obesity is an important risk factor for breast cancer (BC). Patients with this neoplasm and obesity have a worse prognostic factor with higher rates of metastasis, increased resistance to conventional treatments and lower survival rates. A better understanding of the role of obesity, genetic alterations and its molecular pathways is extremely important for the prevention and more individualized treatment of BC in overweight women. E-cadherin, synthesized from the CDH7 gene (gene APC/C activator protein cadherin-1) and Vimentin are proteins involved in cell adhesion and are important in the progression and risk of metastasis of BC. Both VEGF (vascular endothelial growth factor) and AKT (protein kinase B) play important roles in progression and response to treatment while interleukins (IL), especially IL-17B and IL-8, are associated with inflammatory processes and cancer. Objectives: To evaluate the role of genetic alterations and inflammatory molecular pathways of obesity in BC by gene expression (RT-PCR) and protein expression (IHC). Casuistry and Methods: We selected patients according to body mass index (BMI) - with obesity those with BMI > 30 Kg/m? and without obesity those with BMI < 30 kg/m? - and the result of the pathology (invasive ductal carcinoma or benign) and the patients were divided into four groups: group 1 (CM with obesity), group 2 (control with obesity), group 3 (CM without obesity) and group 4 (control without obesity) for analysis of gene expression of CDH1, VIM, IL17B and IL8. Among patients with BC, we selected patients with obesity (group 1a) and without obesity (group 3a) for analysis of Ecadherin, Vimentin, VEGF and AKT protein expression. Results: In the evaluation of the RT-PCR results, in the comparison between groups 1 and 3, we found no significant difference in the expression of genes CDH1 (95% CI -2.228 to 0.8815, p = 0.3771), VIM (95% CI -1.460 to 0.906, p = 0.6266), IL17B (95% CI -2.640 to 5.329, p = 0.5005) and IL8 (95% CI - 2.625 to 2.086, p = 0.8195). In the evaluation of the IHC results, in the comparison between groups 1a and 3a, we found lower protein expression of E-cadherin (95% Cl from 13.08 to 30.51, p < 0.0001) and higher protein expression of Vimentin ( 95% CI -45.46 to -28.40, p < 0.0001), VEGF (95% CI -45.00 to -27.00, p < 0.0001) and AKT (95% CI - -37.72 to -18.89, p < 0.001) in patients with obesity. Conclusions: The lower expression of E-cadherin and the higher expression of Vimentin, VEGF and AKT in patients with BC and obesity indicate that obesity not only increases the risk of developing BC, but also worsens the prognosis of the disease, increases the risk of proliferation and tumor invasion. Although we found no significant difference in gene expression between groups, we observed individual variations that highlight the heterogeneity of obesity