| Background Prostate Cancer(PCa) is the most common cancer in male. Recently, minimally invasive argon-helium cryoablation and immunotherapy have become one of the international forefront of research in PCa. Th17 cells, Treg cells and IL-17, TGF-β are closely related to tumor incidence and development. However, the research about the predictive value of Th17 cells, Treg cells and IL-17, TGF-β factors in prostate cancer and the relationship with the clinical stage and cryotherapy treatment has not been reported.Objective Our study aimed to explore the correlation between the expression of Th17 cells, Treg cells and the related factor IL-17 and TGF-β in peripheral blood with the growth and development of prostate cancer, and to provide clues for the clinical value of these cell and factors in prognosis and the theraptic effect of prostate cancer.Materials and Methods 30 patients with prostate cancer, 20 patients with benign prostatic hyperplasia and 20 normal male adults were included in our study during January 2014 to 2014 December in Tianjin Medical University Cancer Hospital Interventional Radiology. We collected the peripheral blood of all these people. For the prostate cancer patients, we collect the peripheral blood before cryoablation therapy and after surgery at 7th day, 14 th day and 21 st day. We detected the expression of Th17 cells and Treg cells using Flow cytometry method and the related factor IL-17 and TGF-β by ELISA method. The difference of their expression among the prostate cancer, benign prostatic hyperplasia and normal control, the correlation with clinical factors were analysed. Besides, we investigated the changes in the expression of the Th17 cells, Treg cells and IL-17 and TGF-β after cryoablation therapy and the relationship between their expression and PSA remission rate after therapy.Results 1. Th17, Treg and Th17 / Treg ratio: Compared with benign prostatic hyperplasia and normal control group, prostate cancer Th17 cells in peripheral blood was significantly lower(2.09% vs. 6.81% vs. 6.71%, F= 36.71, P<0.0001); however, higher than theproportion of Treg cells in benign prostatic hyperplasia and normal control group(5.40% vs. 2.56 vs. 2.45%, F = 23.88, P<0.0001); Th17 / Treg ratio below the BPH group and normal control group(0.43 vs. 3.45 vs. 3.51, F = 29.68, P <0.0001). 2. Cytokine IL-17 and TGF-β: Compared with benign prostatic hyperplasia and normal control group, prostate cancer in peripheral blood IL-17 levels were significantly lower(19.74 vs. 28.39 vs. 30.36, F = 65.20, P <0.0001); however, TGF-β levels higher than BPH and normal control group(29.35 vs. 13.86 vs. 13.85, F = 117.3, P <0.0001). 3. Factors and Clinical Relevance:(1) Age: Prostate cancer <65 years with prostate cancer group> 65 years compare, Th17 cell ratio(2.48% vs. 1.83%, t = 1.229, P> 0.05); Treg cell percentage(5.16% vs. 5.57%, t == 0.6211, P> 0.05); Th17 / Treg ratio(0.45 vs. 0.42, t = 0.3061, P> 0.05); IL-17 levels(19.75 vs. 19.74, t = 0.0023, P> 0.05); TGF- β levels(2.48 vs. 1.83, t = 0.7900, P> 0.05).(2) T stage: Prostate cancer T2 / T3 / T4 Comparison, Th17%(2.17% vs. 2.30% vs. 1.38%, F = 0.5789, P = 0.5673, P> 0.05); Treg%(5.23% vs. 5.15% vs. 5.52%, F = 0.1174, P = 0.8897, P> 0.05); Th17 / Treg ratio(0.48 vs. 0.46 vs. 0.27, F = 0.6406, P = 0.5354, P> 0.05); IL-17(ng / ml) levels(22.43 vs. 18.88 vs. 18.27, F = 33.68, P <0.0001), where the T3, T4 Comparative T2 period, a significant difference(P <0.05); TGF-β(ng / ml) level(17.61 vs. 24.21 vs. 32.58, F = 23.67, P <0.0001), which compares with T3 and T4 period, a significant difference(P <0.05).(3) Gleason score: prostate cancer Gleason score 2-6,7,8-10 group, Th17%(3.43 vs. 2.28 vs. 1.68, F = 5.006, P <0.05); Treg%(4.3 vs. 6.08 vs. 6.42, F = 5.088, P <0.05); Th17 / Treg ratio(0.77 vs. 0.37 vs. 0.32, F = 4.355, P <0.05); IL-17 levels(20.55 vs. 20.03 vs. 19.38, F = 0.7213, P> 0.05); TGF-β levels(24.56 vs. 30.11 vs. 30.69, F = 2.549, P> 0.05).(4) Pelvic lymph node metastasis: metastasis group and no metastasis, Th17 cell ratio(2.21% vs. 1.88%, t = 0.5852, P> 0.05); Treg cell percentage(6.02% vs. 5.06%, t = 0.5042, P> 0.05); Th17 / Treg ratio(0.35 vs. 0.55, t = 1.726, P> 0.05); IL-17 levels(19.10 vs. 20.85, t = 0.5852, P> 0.05); TGF-β levels(30.75 vs. 26.93, t = 1.693, P> 0.05).(5) Bone metastases: prostate cancer bone metastasis and without bone metastases group, Th17 cell ratio(2.27% vs. 1.67%, t = 1.059, P> 0.05); Treg cell percentage(5.51% vs. 5.16%, t = 0.5024, P> 0.05); Th17 / Treg ratio(0.36 vs. 0.47, t = 0.9230, P> 0.05); IL-17 levels(19.38 vs. 20.60, t = 1.464, P> 0.05); TGF-β levels(30.72 vs. 25.05, t = 2.499, P> 0.05).(6) The prostate specific antigen(PSA): prostate cancer <20ng/ml group with prostate cancer> 20ng/ml group, Th17 cell ratio(2.32% vs. 1.74%, t = 0.8805, P> 0.05); Treg cells ratio(5.06% vs. 5.63%, t= 0.8805, P>0.05); Th17/Treg ratio(0.41 vs. 0.33, t = 1.188, P>0.05); IL-17 levels(20.68 vs. 19.12, t = 2.058, P <0.05); TGF-β levels(25.48 vs. 31.94, t = 3.259, P<0.05).(7) Alkaline phosphatase(ALP): prostate cancer <150U/L group and prostate cancer> 150U/L group, Th17 cell ratio(2.18% vs. 2.02%, t = 0.7849, P> 0.05); Treg cells ratio(5.12% vs. 5.62%, t=0.7849, P> 0.05); Th17/Treg ratio(0.32 vs. 0.38, t = 0.8412, P> 0.05); IL-17 levels(20.53 vs. 19.14, t = 1.824, P> 0.05); TGF-β levels(26.17 vs. 31.78, t = 2.748, P> 0.05). 4.Cryoablation effect: before cryoablation, seven days after surgery, 14 days, 21 days comparison, Thl7%(2.09% vs. 5.12% vs. 6.55% vs. 2.27%, F = 8.038, P<0.0001); Treg%(5.40% vs. 4.54% vs. 1.70% vs. 4.88%, F = 33.66, P<0.0001); Th17/Treg ratios are(0.43 vs. 1.33 vs. 5.94 vs. 0.53, F=13.45, P<0.0001); IL-l7 expression levels were(19.74 vs. 19.88 vs. 28.42 vs. 19.70, F=124.3, P<0.0001); TGF-β expression levels were(29.35 vs. 26.31 vs. 17.77 vs. 31.52, F = 39.3, P <0.0001), prompt Th17%, IL-17 and Th17/Treg ratio increased after the first 14 days reached a peak, but tended to decrease with time, while Treg%, TGF- β decreased after surgery, the first 14 days to a minimum, but tended to increase with time. 5.Clinical prognosis: And clinical prognosis: prostate cancer cryoablation surgery, PSA remission and non-remission group PSA, Th17%(2.21% vs. 1.90%, t=0.5790, P = 0.5172, P>0.05); Treg%(5.47% vs. 5.31%, t=0.2394, P>0.05); Th17/Treg ratio(0.44 vs. 0.43, t = 0.07910, P> 0.05); IL-17(ng / ml) levels(20.11 vs. 19.5, t = 0.7538, P>0.05); TGF-β(ng/ml) level(29.51 vs. 29.11, t=0.1723, P>0.05); PSA decline>80% group and 50%-80% reduction in PSA group, Th17%(2.38% vs. 1.62%, t=2.295, P<0.05); Treg%(4.12% vs. 5.74%, t=1.782, P>0.05); Th17/Treg ratio(0.59 vs 0.32,t=2.715, P<0.05); IL-17(ng/ml) levels(21.65 vs. 18.71,(21.65 vs. 18.71, t = 2.770, P <0.05); TGF-β(ng / ml) levels(28.00 vs. 30.91, t = 1.102, P> 0.05).Conclusion 1. Compared with benign prostatic hyperplasia group and normal control group, Thl7%, Th17/Treg and IL-l7 in peripheral blood of prostate cancer group was significantly lower, while Treg% and TGF- β were significantly higher. The low level of Th17%, IL-17 and Th17/Treg ratio in the peripheral blood of patients were related with high Gleason score and high clinical stage. What’s more, IL-17 expression was negatively related with pelvic lymph node metastasis and PSA level, and TGF-β was positively associated with Gleason score, clinical stage, bone metastasis, PSA and ALP level. 2. After cryoablation treatment, Th17%, IL-17 and Th17/Treg ratio peaked at 14 th day, but decreased at 21 st day postoperatively. Treg% and TGF-β falled to the lowest point at the 14 th day after Cryoablation, but increased at 21 st day postoperatively. 3. Three months after cryoablation group PSA remission and no remission, preoperative Th17%, Treg%, Th17 / Treg ratio, expressing IL-17 and TGF-β, and no significant difference; but we will ease PSA group divided according to the magnitude of decline in PSA PSA decline> 80% PSA group and decreased by 50%-80% between the two groups, Th17%, Th17 Treg expression ratio preoperative / and IL-17, there are significant differences, while Treg%, TGF-β, although there is a certain trend, but no significant difference; we may be prompted to preoperative Th17%, Treg%, Th17 / Treg ratio and related factors IL-17, TGF-β is used to predict the efficacy of cryoablation therapy,It may have clinical significance. |
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