Primary Study On Expression Of PD-1/PD-L1 And HLA-G In Urothelial Carcinoma After Renal Transplantation

Objective Existing studies have demonstrated that programmed death 1(PD-1),programmed death-ligand 1(PD-L1)and human leucocyte antigen-G(HLA-G)can reduce human immune function in a variety of ways.Domestic and foreign researches have also been found that the expression of PD-1,PD-L1 and HLA-G in peripheral blood of transplant recipients were also up-regulated.This may be related to the maintenance of immune tolerance and the prevention of rejection in normal transplant recipients.However,there is no research on whether PD-1,PD-L1 and HLA-G are associated with the high incidence of urothelial carcinoma after transplantation.The aim of this study was to investigate the differences and correlations of PD-1,PD-L1 and HLA-G expression in the three groups,as well as the relationship between the clinical and pathological parameters of the patient,looking for a balance between the the prevention of transplant rejection and reduce the incidence of tumor after transplantation of immunosuppressive agents,and provide a new idea for the prevention and treatment of urinary tract epithelium tumor after transplantation.Methods To consult the medical records of urothelial carcinoma after renal transplantation in Tianjin First Central Hospital from January 1,2005 to September 30,2016,Thirty-two patients who with urothelium carcinoma for the first time after renal transplantation(RTUC)were selected as the experimental group.Thirty-two non-transplanted patients with urothelial carcinoma(NTUC)and ten healthy adults as the control group,normal urinary tract epithelial from the ten healthy adults(NUTE).Immunohistochemical(IHC)method was used to detect the expression of PD-1,PD-L1 and HLA-G in tissue of the three groups.SPSS 22.0 software was used for data analysis,with P<0.05 as the difference between the statistical criteria.Results(1)The expression rates of PD-1 in group RTUC,NTUC and NUTE were 53.13%,56.25% and 10.00% respectively.The positive expression rates of PD-L1 in group RTUC,NTUC and NUTE were 65.63%,59.38% and 0% respectively.The results showed that the expression rate of PD-1 and PD-L1 in group RTUC was similar to group NTUC(P>0.05).The expression of PD-1 and PD-L1 in group RTUC and NTUC were significantly higher than that in group NUTE(P<0.05);(2)The expression of PD-1 was 60.71% in the high-grade urothelial carcinoma of the group RTUC and no expression in the low-grade urothelial carcinoma(P=0.038),suggesting that the expression of PD-1 was related to the pathological grade;The expression rate of PD-L1 in T2-T4 patients in RTUC was significantly higher than that in patients with Ta-T1 stage(80.95% vs 36.36%,P=0.020),suggesting that the expression of PD-L1 was correlated with clinical stage;(3)The expression of PD-1 in RTUC was not related to age,sex,tumor location,clinical stage and lymph node status.The expression of PD-L1 in RTUC was not correlated with age,sex,tumor location,tumor grade and lymph node status;(4)The positive expression rates of HLA-G in the group RTUC,NTUC and NUTE were 75.00%,37.50% and 0% respectively.The results suggest that the expression rate of HLA-G in group RTUC was significantly higher than that in group NTUC(P=0.001).The expression of HLA-G in the urothelial carcinoma groups whether underwent renal transplantation were both higher than that in NUTE(P<0.05);(5)The expression of HLA-G in group RTUC was not correlated with age,sex,tumor location,clinical stage,pathological grade and lymph node status(P>0.05);(6)The expression rates of PD-1,PD-L1 and HLA-G in group RTUC who used FK506 were both higher than those used Cs A(P>0.05);(7)The correlation analysis between PD-1,PD-L1 and HLA-G expression in group RTUC and NTUC showed no significant correlation(P>0.05).Conclusion PD-1 and PD-L1 may play an important role in the development and progression of urothelial carcinoma,and HLA-G may may contribute to the formation of urothelial carcinoma after renal transplantation.The expression of HLA-G in urothelial carcinoma after renal transplantation in this study provides a preliminary theoretical basis for finding the balance between the transplant rejection and the reduction of the incidence of postoperative malignant tumor after renal transplantation,which also provides a new idea for the prevention and treatment of urinary tract epithelial tumor after transplantation.