Correlation Between Periprostatic Adipose And Prostate Cancer Aggressiveness

PART I Influence of adipocytokines and periprostatic adiposity measurement parameters on prostate cancer aggressivenessObjective: To evaluate the correlation between aggressiveness of prostate cancer(CaP) and obesity measuring the periprostatic fat on magnetic resonance imaging(MRI); To study the relevance of adipocytokines with prostate cancer aggressiveness.Patients and method: A total of 184 patients who underwent radical retropubic prostatectomy(RRP) were analyzed retrospectively; According to Carrlo PR, the patients were stratified into three groups; The clinical and pathologic information were gathered. The different fat measurements(periprostatic fat area(PFA), the subcutaneous fat thickness(SFT), the anterior and posterior abdominal fat thicknesses(AAT,PAT) and anteroposterior diameter(APT)) were performed on the slices of MRI;CRP was measured with blood routine test by the clinical laboratory. 3 ml of serum was separated from each participant’s blood sample, and then measured the level of IL-6, leptin by ELISA. The different fat measurement measured on the slice of MRI and the levels of adipocytokines were compared with the clinical and pathologic factors using spss ver.13.0;Result: 1. The median age, prostate volume, T-zone volume, bleeding volume and duration of operation have no significant differences among three groups(p>0.05). BMI at the time of RRP was 25.51±2.46, 25.83±2.16 and 25.74±2.29, respectively(no significance, p=0.142).The PFA and Ratio showed a statistically significance(p=0.019, 0.025) among three groups; However, no differences in terms of SFT, AAT, PAT and APT were observed among the three groups(P=0.773,0.533,0.800,0.387). In clinical stage, the PFA and Ratio showed a statistically significance(P=0.014, 0.037). In terms of Gleason score, nothing but “PFA” fat measurement was found to have difference between two groups(P=0.017). Moreover, the prostate volume and T-zone volume have statistically significance(P=0.049, 0.020). BMI was found no difference between two groups(P=0.451, 0.576); patients with bleeding volume over 450 ml were significantly older(P=0.022) and had more dispose in periprostate area(Ratio: 88.46±3.00 VS 86.95±4.36, p=0.013). The PAT,APT and ratio was significantly higher in the group of operation time>210min(P=0.015, 0.041, 0.042).Logistic regression analysis adjusted for age revealed a statistically association between the PFA, the Ratio and the risk of having high-risk disease(p=0.031, 0.024). 2. The level of IL-6, Leptin and CRP significantly increased with the aggressiveness of prostate cancer. The strongest correlation was seen between IL-6 and PFA(Pearson r coefficient=0.67, P<0.001). No relevant was seen between IL-6 and BMI(Pearson r coefficient=0.03,P=0.70); The Leptin was statistically relevant with PFA and Ratio(Pearson r coefficient=0.35, 0.37; P=0.008, 0.006). No relevant was also seen between Leptin and BMI(Pearson r coefficient=0.08, P=0.27); A clear relevant was seen between CRP and PFA/Ratio(Pearson r coefficient=0.50, 0.49, P=0.002, <0.001). CRP was no associated with BMI(Pearson r coefficient=0.02, P=0.58).Conclusion: 1. The Periprostatic adipose affects the prostate cancer aggressiveness, and predicts risk of prostate cancer as an impact factor. 2. The Periprostatic adipose have effect in accurate evaluation of stage and grade of CaP 3. The periprostate adipose could increase the difficulty and risk of RRP, mainly representing bleeding volume and operation time 4. The Periprostatic adipose influences the secretion of adipocytokines, such as IL-6, PFA and CRP, which have promoting effect on the progression of prostate cancer. 5. MRI is proved to be a precise way to measure the periprostate adipose. We should not only evaluate the stage and grade of CaP, but also predict the prognosis of patient with RRP by measuring periprostatic adiposity on pre-operative MRI.PART II The experimental research between adipocytokines in Periprostatic adipose and prostate cancer aggressivenessObjective: This study aims to analyze the expression level of IL-6、Leptin and Adiponectin in different stage and grade periprostatic adipose by immunohistochemistry and Real-time quantitative PCR(Q-PCR);So as to preliminarily discover the mechanism that the periprostatic adipose affects the prostate cancer aggressiveness.Patients and method: The periprostatic adipose tissues were collected from 30 patients who underwent radical retropubic prostatectomy(RRP). According to Carrlo PR, the patients were stratified into three groups. The control group was collected from 10 patients who underwent radical cystectomy. The expression level of IL-6、Leptin and Adiponectin was detected by immunohistochemistry in periprostatic adipose tissues;Them RNA expression level of IL-6、Leptin and Adiponectin was tested by Real-time quantitative PCR(Q-PCR) in periprostatic adipose tissues.Result: 1. The results of immunohistochemistry showed that IL-6、Leptin and Adiponectin were expressed in the periprostatic adipose tissues. There were significant differences in the positivity rates of IL-6 expression in the periprostate adipose between prostate cancer and control( Χ2=15.873,P<0.001).The intensity of IL-6 expression had statistically significance between two groups(Z=-2.831,P=0.005);The expression level of IL-6 significantly increased with the aggressiveness of prostate cancer(Χ2=13.914,P=0.001), and The intensity of IL-6 expression was statistically relevant with the prostate cancer aggressiveness(rs=0.668,P<0.001);The positivity rates of Leptin expression in the periprostate adipose showed a statistically significance between prostate cancer and control(Χ2=4.596,P=0.032), and the intensity of Leptin expression was found no difference between two groups(Z=-1.712,P=0.085);No differences in the expression level of Leptin were observed among the three groups(Χ2=3.590,P=0.166), and no relevant was also seen between the intensity of Leptin expression and the prostate cancer aggressiveness(rs=0.351,P=0.057); There were significant differences in the positivity rates of Adiponectin expression in the periprostate adipose between prostate cancer and control(Χ2=8.547,P=0.003),and the intensity of Adiponectin expression had statistically significance between two groups(Z=-3.387,P=0.004) 。 The expression level of Adiponectin have no significant differences among three groups(Χ2=2.199,P=0.333),the intensity of Adiponectin expression was no associated with the prostate cancer aggressiveness(rs=-0.263,P=0.161). 2. The results of Q-PCR showed IL-6 m RNA、Leptin m RNA and adiponectin m RNA were expressed in the periprostatic adipose tissues; The m RNA expression of IL-6 in periprostatic adipose tissues of prostate cancer was higher than that of control(1.000±0.220VS2.915±1.805,P=0.049);The m RNA expression of IL-6 showed a statistically significance among three groups(P=0.007); The IL-6 m RNA expression in high-risk group is higher than that in low-risk group(P=0.002),and no differences in the IL-6 m RNA expression were observed between high-risk group VS intermediate-risk group and intermediate-risk group VS low-risk group(P=0.141,P=0.103). There were no significant differences in the Leptin m RNA expression in the periprostate adipose between prostate cancer and control( 1.000±0.276VS2.073±0.444,P=0.431); Nodifferences were observed in the Leptin m RNA expression among three groups(P=0.703);The m RNA expression of Adiponectin in periprostatic adipose tissues of prostate cancer was lower than that of control(0.1366±0.046VS1.000±0.089,P<0.0001);No differences were observed in the Adiponectin m RNA expression among three groups(P=0.218);Combined the low-risk group with the intermediate-risk group, a clear differences was seen compared to high-risk group.( 0.201±0.065VS0.034±0.021, P=0.018)。Conclusion: 1. IL-6、Leptin and Adiponectin were expressed in the periprostatic adipose tissues, which constitute the microenvironment of prostate cancer aggressiveness. 2. The expression level of IL-6 was obviously higher in the periprostate adipose of prostate cancer, and statistically relevant with the prostate cancer aggressiveness; IL-6 may promote the aggressiveness of prostate cancer by autocrine and paracrine. 3. No relevant was also seen between Leptin expression and the prostate cancer aggressiveness; Leptin may influence the aggressiveness of prostate cancer by endocrine, which secrete into blood and is combined with receptor in the surface of prostate cancer cell. 4. The expression level of Adiponectin was obviously lower in the periprostate adipose of prostate cancer; Adiponectin is a protective factor, which may influence the aggressiveness of prostate cancer by autocrine and paracrine.PART III The difference of adipocytokines mR NA expression in subcutaneous adipose、 periprostate adipose and prostate cancer tissueObjective: This study aims to compare the m RNA expression level of IL-6、Leptin and Adiponectin in subcutaneous adipose、 periprostate adipose and prostate cancer tissue from the same patient,so as to preliminarily investigate the characteristic of IL-6、Leptin and Adiponectin m RNA expression in difference tissues.Patients and method: The periprostatic adipose tissues and prostate cancer tissue were collected from 10 patients who underwent radical retropubic prostatectomy(RRP). The m RNA expression level of IL-6 、 Leptin and adiponectin was tested by Real-time quantitative PCR(Q-PCR) in subcutaneous adipose、 periprostate adipose and prostate cancer tissue from the same patient.Result: The results of Q-PCR showed IL-6 m RNA、Leptin m RNA and adiponectin m RNA were expressed in subcutaneous adipose、 periprostate adipose and prostate cancer tissue from the same patient. IL-6 m RNA expression in periprostate adipose was significantly higherthan that in subcutaneous adipose(1.804±0.093VS1.000±0.013,P<0.001); IL-6 m RNA expression in prostate cancer tissue was also significantly higher than that in subcutaneous adipose( 1.703±0.096VS1.000±0.013, P=0.001), but IL-6 m RNA expression in periprostate adipose was similar with prostate cancer tissue(1.804±0.093VS1.703±0.096,P=0.062);IL-6 m RNA expression in periprostate adipose was positively correlated with that in prostate cancer tissue(r=0.663,p=0.036);No relevant was seen between IL-6 m RNA expression in prostate cancer tissue and that in subcutaneous adipose(r=-0.317,p=0.372);Leptin m RNA expression in prostate cancer tissue was significantly higher than that in subcutaneous adipose(1.780±0.108VS1.000±0.073,P=0.005),and also significantly higher than that in periprostate adipose(1.780±0.108VS1.152±0.143,P=0.003),but no differences in Leptin m RNA expression were observed between periprostate adipose and subcutaneous adipos(e1.152±0.143VS1.000±0.073,P=0.101);Leptin m RNA expression in periprostate adipose was no associated with that in prostate cancer tissue(r=-0.527,p=0.117);No relevant was also seen between Leptin m RNA expression in subcutaneous adipose and that in prostate cancer tissue(r=-0.551,p=0.099);Adiponectin m RNA expression in prostate cancer tissue was significantly lower than that in periprostate adipose(0.894±0.143VS1.126±0.126,P=0.006),but was similar with that in subcutaneous adipose(0.894±0.143VS1.000±0.120,P=0.071);no differences in Adiponectin m RNA expression were observed between periprostate adipose and subcutaneous adipose(1.126±0.126VS1.000±0.120,P=0.072). Adiponectin m RNA expression in periprostate adipose was positively correlated with that in prostate cancer tissue(r=0.707,p=0.022);No relevant was seen between Adiponectin m RNA expression in prostate cancer tissue and that in subcutaneous adipose(r=0.534,p=0.112).Conclusion: 1. IL-6 m RNA、Leptin m RNA and adiponectin m RNA were expressed in subcutaneous adipose、 periprostate adipose and prostate cancer tissue from the same patient. 2. IL-6 m RNA expression in periprostate adipose was significantly higher than that in subcutaneous adipose and positively correlated with that in prostate cancer tissue, showing that IL-6 expressed higher in periprostate adipose may be the chief mechanism of periprostate adipose promoting the aggressiveness of prostate cancer. 3. Leptin m RNA expression in prostate cancer tissue was significantly higher than that in subcutaneous adipose and periprostate adipose, but no differences in Leptin m RNA expression were observed between periprostate adipose and subcutaneous adipose,indicating that Leptin expressed highly in patients of prostate cancer may be correlated with subcutaneous adipose、periprostate adipose and prostate cancer tissue, which may result in the aggressiveness of prostate cancer. 4. Adiponectin m RNA expression in prostate cancer tissue was significantly lower than that in periprostate adipose, and Adiponectin m RNA expression in periprostate adipose was positively correlated with that in prostate cancer tissue. 5. There might be intimate relationship between periprostate adipose and prostate cancer tissue of IL-6 and Adiponectin expression.