Avaliação da atividade de enzimas do sistema purinérgico e de biomarcadores inflamatórios em pacientes com câncer de bexiga não invasivo

Abstract

According to global data, bladder cancer (BC) is the sixth most common and lethal type of tumor in the male population. Its occurrence is particularly associated with smoking, presenting a concerning morbidity and mortality profile in terms of public health, including in Brazil. Inflammatory processes and purinergic signaling can directly influence bladder carcinogenesis as well as tumor progression. The enzymatic action of ectonucleotidases and the tissue response to adenine nucleotides and nucleosides play a significant role and should be increasingly explored. Considering this interrelation with BC, the present study aimed to evaluate the activity of purinergic system enzymes in patients with non-invasive BC and the levels of some inflammatory biomarkers in these patients. This study is characterized as a quantitative, cross- sectional observational study. Platelet, serum, and plasma samples were collected through venipuncture (30 mL of blood) from 29 patients diagnosed with BC, before the initiation of any therapeutic intervention, and from 36 control individuals of a similar age group. The activities of the enzymes E-NTPDase, E-5’-nucleotidase, and Adenosine Deaminase (ADA) were evaluated, as well as the serum levels of IL-4, IL-6, and IL-10. The collection of biological material from the patients was carried out at the facilities of the Regional Hospital of the West, located in Chapecó/SC. Clinicopathological information from the patients was obtained from medical records. For statistical analyses, the data were first tested for normality using the Shapiro-Wilk test. Subsequently, Student’s t-test and One-way ANOVA were applied. The significance level used was 0.05, and the statistical program used was GraphPad Prism 8.0.1. The patients involved in the study had a mean age of 69 years, and regarding the clinical staging of BC, 18 (62.06%) were classified as Stage 0 and 11 (37.94%) as Stage 1. E-NTPDase activity for ATP and ADP hydrolysis, as well as E-5’-nucleotidase activity for AMP hydrolysis, was significantly increased in patients with Stage 0 and Stage 1 compared to the control group. Regarding ADA, its activity was substantially decreased in Stage 0 and Stage 1 compared to the control group. Plasma levels of IL-10, IL-6, and IL-4 were higher in patients with non- invasive BC compared to the control group. BC was shown to be one of the most common and lethal tumors, particularly among older male smokers. Tumor presence favors an increase in extracellular ATP levels, activating the cascade of enzymes responsible for the hydrolysis of this nucleotide and its products. The overactivation of E-NTPDase and E-5’-nucleotidase is associated with a poorer prognosis for BC, just as lower ADA activity favors the accumulation of adenosine (Ado) in the body, an important immunosuppressive molecule that facilitates the escape of tumor cells from immune surveillance. Moreover, patients with non-invasive BC present elevated levels of IL-4, IL-6, and IL-10, molecules related to tumor development and metastasis, in addition to smoking, a factor that greatly contributes to BC incidence. The results showed that BC directly alters the activity of purinergic system enzymes and serum inflammatory markers. These findings contribute to a better understanding of purinergic signaling and inflammatory processes in BC pathophysiology, becoming an important tool for monitoring and treating these patients.