Serum concentration of interleukin-35 and its association with tumor stages and FOXP3 gene polymorphism in patients with prostate cancer.

IL-35 is an immunosuppressive cytokine that is largely synthesized by regulatory T (Treg) cells and may inhibit antitumor immune responses. This investigation aimed to determine the serum IL-35 concentrations and a single nucleotide polymorphism (SNP) in position of rs3761548, within the promoter region of FOXP3 gene, in patients with prostate cancer (PC). The blood specimens were obtained from 150 PC patients prior to using radiation therapy, chemo- or immunotherapy and 150 age-matched healthy men as a control group. The serum IL-35 concentrations and the pattern of genetic variation at position of rs3761548 were assessed using ELISA and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), respectively. The mean serum IL-35 concentrations were significantly higher in PC patients when compared with healthy control group (20.01 ±â€¯7.03 Pg/mL vs. 11.60 ±â€¯2.49 Pg/mL, P < 0.001). The serum IL-35 concentrations raised with progression of PC stages so that there was a significant difference between PC stages concerning the IL-35 concentrations (P < 0.001). The mean serum IL-35 concentrations in patients with Gleason scores of 1-6 and Gleason scores 7-10 were significantly higher as compared with healthy controls (P < 0.001). Moreover, the serum IL-35 concentrations in patients with having Gleason scores of 7-10 were significantly higher as compared with patients with Gleason scores of 1-6 (P < 0.001). Evaluation of the genetic variations in position SNP rs3761548 revealed that the AA genotype and A allele were more prevalent whereas CC genotype and C allele were less prevalent in PC patients when compared with healthy men (P < 0.01, P < 0.001, P < 0.002 and P < 0.001, respectively). The AA genotype and A allele were associated with higher risk of PC incidence [OR: 2.42 (95% CI: 1.179-4.99); P < 0.001 and OR: 1.732 (95% CI: 1.244 - 2.413); P < 0.001, respectively]. The mean serum IL-35 concentrations were significantly higher in total subjects (PC patients + healthy individuals) with AA genotype and A allele than individuals with CC genotype and C allele at SNP rs3761548 (P < 0.05 and P < 0.01, respectively). Higher serum IL-35 concentrations observed in patients with PC that were increased with progressive tumor stages. These findings indicate that the IL-35 is possibly involve in tumor progression. Moreover, SNP rs3761548 may affect the susceptibility to PC and the serum IL-35 concentrations.

Expression of proapoptotic receptors Fas/Fas-L on sperm cells and levels of their soluble forms in seminal fluid from patients with varicocele.

Varicocele is a condition in which the pampiniform venous plexus in the scrotum dilates abnormally during puberty, affecting testicular growth and semen parameters, and is thought to be a major cause of male infertility. The findings of researches on the presence of the Fas system in sperm are controversial. As the main triggers of apoptosis in the semen of patients with varicocele, in this study, we examined the expression of Fas/Fas-L on sperm cells and also the levels of their soluble forms in seminal plasma. Semen samples were taken from 45 patients with varicocele (study group) and 45 healthy subjects without varicocele (control group) after 3-5 days of ejaculatory abstinence. Flow cytometry was used to examine the expression of Fas and Fas ligand (Fas-L) on Sperm cells. Furthermore, soluble Fas (sFas) and soluble Fas-Ligand (sFas-L) levels in the seminal fluid were determined using an ELISA (enzyme-linked immunosorbent assay). The presence of Fas and Fas-L proteins on the sperm ejaculation surface was not found in the patients with varicocele or the control groups. However, in the case group (3.32 ± 0.31 ng/mL), sFas seminal concentrations were slightly lower than in the control group (5.50 ± 0.36 ng/mL) (p < 0.001). In varicocele patients, there was a strong negative association between seminal sFas and sperm motility. Apoptosis effects through this system on key sperm parameters were not found based on our findings. In varicocele, a reduction in sperm count and motility does not seem to be due to Fas-related mechanisms, but rather to other mechanisms.