Atividade das enzimas do sistema purinérgico e sua associação com os níveis de PSA, o escore de Gleason e a classificação tumoral em pacientes com câncer de próstata

Abstract

Changes in the morbidity and mortality profile of prostate cancer (PC) in recent decades have made this pathology a public health problem in several countries, including Brazil. Inflammatory processes and purinergic signaling can directly influence prostate carcinogenesis, as well as tumor progression. The enzymatic action of ectonucleotidases and the response of tissues to nucleotides and adenine nucleoside play a fundamentally important role, and should be increasingly explored. Considering this interrelation with PC, the objective of the present study was to evaluate the activity of E-NTPDase and Adenosine deaminase (ADA) in patients with PC and its association with serum levels of PSA (Prostate Specific Antigen), the score of Gleason, tumor staging and ISUP scale (International Society of Urological Pathology) of these patients. This is a cross-sectional observational quantitative study associated with a qualitative approach. For the statistical analyses, firstly, the data were tested for normality by applying the Shapiro-Wilk test. Afterwards, Student's t test and One-way ANOVA were used. The significance level used was 0.05 and the statistical program used was GraphPad Prism 8.0.1. Lymphocyte samples were collected by venipuncture (30 mL) from 39 patients diagnosed with PC, prior to surgical treatment of the tumor, and from 37 control individuals, of similar age range. After the invitation and acceptance to participate in the study, the participants signed the Term of Free and Informed Consent to participate in it. From the analysis of the results, it was possible to observe that in relation to age, the mean was 66 ± 6.72 years in patients, and 65.81 ± 10.30 in controls (p=0.8503). Of the group of patients, 21 (54%) had serum PSA levels ≥4 to ≤10 ng/mL before the therapeutic intervention. Regarding the Gleason score, 27 (69.2%) patients had a score of 7. Regarding clinical staging, 17 (43.6%) patients had a T2 classification, and 14 (35.9%) had a T3 classification. Regarding the ISUP score, 19 (48.8%) patients had ISUP classification 2. E-NTPDase activity, for the hydrolysis of ATP in lymphocytes, is significantly increased in the group of patients with CP when compared to the control group (p=0.0001). The activity of E-NTPDase, for the hydrolysis of ADP in lymphocytes, is significantly reduced in the group of patients with CP when compared to the control group (p=0.0001). ADA activity in lymphocytes is reduced in patients with CP when compared to the control group (p=0.0003). Regarding serum PSA levels, ATP hydrolysis was statistically higher in patients with CP compared to the control group, in both analyses, serum PSA levels < 10 (p=0.0037) and PSA ≥ 10 (p= 0.0001). ADP hydrolysis was statistically lower in patients with CP compared to the control group when PSA ≥ 10 and PSA < 10, both p-value=0.0001. ADA activity significantly decreased with increasing serum PSA levels compared to the control group, both PSA < 10 (p=0.0104) and PSA ≥ 10 (p=0.0086). Regarding the Gleason score, ATP hydrolysis was higher in the patient group when compared to the control group in both analyses, Gleason <7 (p=0.5664), Gleason 7 (p=0.0001) and Gleason > 7 (0.0056). ADP hydrolysis was lower in the patient group when compared to the control group in both analyses, Gleason <7 (p=0.0034), Gleason 7 (p=0.0001) and Gleason > 7 (0.0012). ADA activity was lower in the patient group when compared to the control group in both analyses, Gleason <7 (p=0.3647), Gleason 7 (p=0.0171) and Gleason > 7 (0.3955). Regarding clinical staging, ATP hydrolysis was increased in the patient group when compared to the control group in both analyses, T1 (p=0.1601), T2 (p=0.0004), T3 (p=0.0003). ADP hydrolysis was reduced in the patient group when compared to the control group in both analyses, T1 (p=03557), T2 and T3 (p=0.0001). ADA activity was reduced in the patient group when compared to the control group in both analyses, T1 (p=0.1877), T2 (p=0.0303), T3 (p=0.0397). Regarding the ISUP scale, ATP hydrolysis was increased in the patient group when compared to the control group in all analyses, ISUP 1 (p=0.2200), ISUP 2 (p=0.0024), ISUP 3 (p=0.0192), ISUP 4 and 5 (p=0.0108). ADP hydrolysis was decreased in the patient group when compared to the control group in all analyses, ISUP 1 (p=0.0005), ISUP 2 and ISUP 3 both (p=0.0001), ISUP 4 and 5 (p =0.0007). ADA activity was reduced in the patient group when compared to the control group in all analyses, ISUP 1 (p=0.0832), ISUP 2 (p=0.0068), ISUP 3 (p=0.2625), ISUP 4 and 5 (p=0.2530). For the first time, it was possible to relate E-NTPDase and ADA activity to serum PSA levels, Gleason score, tumor staging, and ISUP values in patients with CP. In time, additional experiments on the expression of receptors and analyzes in tumor tissue are necessary to corroborate the results found in the present study, so that the modulation of purinergic signaling can form the basis of new drugs and efficient therapeutic protocols in controlling the development and progression of CP.