PD-L1 基因3 ’ UTR单核苷酸多态性与膀胱尿路上皮癌关系的病例对照研究

目的:探讨免疫关卡点分子程序性死亡配体1 (programmed death ligand 1,PD-L1)基因3'端非翻译区(3'untranslated region,3'UTR)单核苷酸多态性(single nucleotide polymorphism,SNP)与膀胱尿路上皮癌(bladder urothelial carcinoma,BUC)发病风险及临床病理特征之间的关系.方法:采用病例-对照研究方法,PCR-LDR技术分别检测2013年6月至2015年12月在青岛大学附属医院泌尿外科住院手术治疗的213例BUC患者和251例同期健康体检者PD-L1基因3'UTR的rs4143815位点和rs2297136位点基因型分布频率,采用卡方检验和非条件多因素Logistic回归分析不同基因型与BUC发病风险以及临床病理特征之间的关系.结果:BUC组PD-L1基因3'UTR的rs4143815位点基因型分布频率与对照组相比存在明显差异,GG基因型个体发生BUC的风险是CC基因型的2.83倍(95％CI:1.82～4.64,P＜0.01),携带G突变基因(CG/GG基因型)个体BUC发病风险是CC型基因个体的1.53倍(95％CI:1.01～2.24,P＜0.01),同时BUC组rs4143815位点携带G突变基因频率与BUC病理分级和临床分期具有相关性(P＜0.05或P＜0.01);而在rs2297136位点,BUC组和对照组基因型分布频率无显著差异,CC、CT及TT基因型个体之间发生BUC的风险亦无显著差异(均P＞0.05).结论:PD-L1基因3'UTR的rs4143815位点SNP与BUC的发病风险和恶性进展可能具有相关性.

Research on clinicopathological relationship of SNP of PD-L1 gene 3'UTR with BUC by case-control studies

Objective:To explore relationship between single nucleotide polymorphism (SNP) of programmed death ligand 1 (PD-L1) gene,an immune checkpoint molecule,3'untranslated region (3'UTR) and onset risk,clinical pathological features of bladder urothelial carcinoma (BUC).Methods:A case-control study was used.Polymerase chain reaction-ligase detection reaction (PCR-LDR) assay was used to detect the genotype distribution frequency ofrs4143815 and rs2297136 locus in PD-L1 gene 3'UTR of the 213 patients with BUC who were hospitalized in Department of Urology Surgery,the Affiliated Hospital of Qingdao University for surgical treatment during June 2013 to December 2015 and the 251 individuals for health examination during the same stage.A relationship between different genotypes and onset risk of BUC as well as clinicopathological features of the patients with BUC was analyzed by chi-square test and unconditionalmultivariate Logistic regression assay.Results:Significant differences of genotype frequencies at the rs4143815loci were found between BUC cases and controls.Onset risk of BUC in the individuals carring GG genotype was 2.83 times (95％CI:1.82-4.64,P＜0.01) of the individuals carring CC genotype and onset risk of BUC in the individuals carting G mutation gene (CG/GG genotype) was 1.53 times (95％ CI:1.01-2.24,P＜0.01) of the individuals carring CC genotype.Furthermore in the BUC group,frequency of carting G mutation gene at the rs41438151oci was significantly correlated to pathological grade of BUC and clinical staging of the patients with BUC (P＜0.05,P＜0.01).However at the rs2297136 loci,any significant difference of gnotype distribution frequency between the BUC group and the control group was not found.Onset risks of BUC among the individuals carting CC,CT and TT genotypes were not obviously different.Conclusion:SNP of rs41438151oci in PD-L1 gene 3'UTR could closely related to onset rick and malignant progression of BUC.