Study On Expression Of MIF Gene In Human Prostate Cancer And Relationship Between Its Single Nucleotide Polymorphisms And Risk Of Prostate Cancer

Part I Expression and clinical significance of macrophage migration inhibitory factor (MIF) in prostate cancerObjective:In this part we want to acquire the expression of MIF mRNA and protein in prostate cancer (PCa) tissue and benign prostatic hyperplasia (BPH) tissue. At the same time we want to know whether MIF protein expression have relationship with the biological behaviors of PCa. We can understand the molecular mechanism of PCa all the better from these expressions.Methods:Immunohistochemistry was used to detect the expression of MIF in PCa (n=60) and BPH (n=20); All dyeing slice was assessed by two pathological doctors in a double-blind method. The score criteria of MIF apply the method of Liangzhong Xu et al. SPSS20.0statistical software was applied to analysis the data and statistical significance was defined as P values less than0.05.Results:In BPH and PCa, the positive rates of MIF was on the rise from20.00%to68.33%respectively, showing significant difference (P<0.01); In Gleason score≤6score,7score and≥8score, the positive rates of MIF was60.60%,66.67%and86.67%respectively, but showing no significant difference (P<0.05); In TNM Ⅰ+Ⅱ and Ⅲ+Ⅳ, the positive rates of MIF was on the rise from54.05%to91.30%respectively, and showing significant difference (P<0.01).Conclusion:The expressions of MIF were more increased in PCa than BPH. Results indicate that MIF was the diagnostic and prognostic index of PCa and it provide theory basis about the gene target therapy in PCa.Part II Expression of MIF in serum of patients with prostate cancer and its clinical significanceObjective:To observe the expression of MIF in serum of patients with prostate cancer and its clinical significance and its correlation with prostate specific antigen (PSA).Methods:The levels of serum MIF were measured by an enzyme-linked immuno sorbent assay (ELISA) in98patients with prostate cancer,56patients with benign prostatic hyperplasia (BPH) and29healthy male adults as healthy controls.Results:The positive rates of MIF in serum of prostate cancer, BPH and healthy controls were100%(98/98),75%(42/56) and70%(20/29) respectively.The MIF levels of patients with prostate cancer were significantly higher than those of the other two groups (P<0.01), But there was no difference in serum levels between BPH and healthy controls (P>0.05). The MIF levels was not correlated with PSA in all serums (r(s)=0.112,P=0.131>0.05,N=183)Conclusions:The levels of MIF were correlated significantly with prostate cancer. MIF may be used as a candidate indicator for diagnosis, therapy and prognosis of prostate cancer. But it can not improve the sensitivity and specificity of PSA in detecting prostate cancer.Part III Association between genetic polymorphism in MIF and risk of prostate cancer in a Chinese populationObjective:This study was designed to detect the association between MIF-173G/C polymorphism and prostate cancer.Methods:Genotypes were determined in98patients with prostate cancer and80controls. The adjusted odds ratios (ORs) and95%confidence intervals (CIs) were calculated.Results:There are3genotypes in the MIF-173G/C polymorphism in Tianjin Han population:GG, CC and GC.The GG is the normol genotype, GC and CC genotypes are the risk factor of PCa. The MIF-173G allele was detected in72.5%of normal controls and59.7%of PCa patients, while MIF-173C allele was detected in0.275of normal controls and0.403of PCa patients. There was significant difference in MIF-173genotype distribution between patients and controls (P<0.05).The genotype frequencies of MIF-173GQ MIF-173GC, MIF-173CC in PCa patients and normal controls were37.7%,43.9%,18.4%and52.5%,40.0%,7.5%, respectively. There was a significant difference in the frequency of genotype between the two groups (P<0.05).The result shows that the GC and CC genotype may be the risk factors of the occurrence of PCa. Compare to the G allele, C allele increases the risk of PCa.Conclusion:There is a polymorphism of MIF-173in Tianjin Han Population. These findings suggest that MIF-173G/C polymorphism may be a genetic susceptibility factor for prostate cancer among Chinese. C allele increases the risk of PCa.