Avaliação de componentes da sinalização purinérgica na progressão e desenvolvimento do câncer de próstata

Abstract

Changes in the morbidity and mortality profile of prostate cancer (PCa) in recent decades have made this pathology a public health problem in several countries, including Brazil. Inflammatory processes and purinergic signaling can directly influence the progression and tumor development of PCa. The action of purinergic signaling components, their receptors and enzymes in the tumor microenvironment of the prostate is of crucial importance due to the sequence of events generated, affecting the molecular mechanisms. Considering this interrelationship with PCa, the objective of the present study was to evaluate the components of purinergic signaling in patients diagnosed with this tumor type. This is a quantitative, observational and cross- sectional study. Blood samples were collected by venipuncture (30 mL) from 39 patients diagnosed with PCa, prior to the beginning of treatment, at the time of surgery to remove the tumor, and from 37 control individuals of a similar age group. The gene expression of the enzymes of the purinergic system CD39 and CD73, and of the P2X7 receptor, in addition to the protein expression of CD39, in lymphocytes of patients and controls, were evaluated. The data generated were analyzed for normality using the Shapiro-Wilk test. Afterwards, the Student's t-test was used for parametric data and the Mann-Whitney test for non-parametric data to make comparisons of expressions between the groups. For the correlations between the variables studied, Pearson's test for parametric data and Spearman's test for non-parametric data were used. The significance level used was 0.05, and statistical analyses were performed using the GraphPad Prism 8.0.1 software. The mean age of the patients with PCa was 66 years, and 74.3% of them were married and 82.1% were nonsmokers. In addition, 87.2% have not had a previous diagnosis of COVID-19, 61.5% did not have diabetes mellitus (DM) or hypertension (SAH), and 84.6% had no family history of PCa in first-degree relatives. As statistically significant results, it was observed the increase in gene expression of the P2X7 receptor (p<0.0260), the enzyme CD39 (p<0.0125) and CD73 (p<0.0268) in the group PCa compared to the control group, as well as the positive correlation between the gene expression of P2X7 and CD39 in the control group (p<0.0266). Through this work, the relevance of the purinergic signaling cascade derived from the tumor process in the prostate can be highlighted, impacting the pro- inflammatory and immunosuppressive patterns of the tumor microenvironment. As future perspectives, exploring purinergic signaling pathways by integrating modulators with existing therapies, such as immunotherapies, may be a good strategy, as well as therapies involving biomarkers related to synergistic signaling pathways to the purinergic system and PCa.