肺腺癌中缺氧诱导因子-1α调控程序性死亡因子配体1的表达  

Role of hypoxia-inducible factor-1α in the regulation of programmed death ligand 1 expression in lung adenocarcinoma

作　　者：张智慧[1] 王丽丽[1] 高华[1] 张健[1] 李娟[1] 李远[1] 武春晓[1] 卢志明[1] 

机构地区：[1]山东大学附属省立医院检验部,山东济南250021

出　　处：《山东大学学报（医学版）》2017年第4期65-70,75,共7页Journal of Shandong University:Health Sciences

基　　金：国家自然科学基金(81372775);山东省医药卫生科技发展计划(2014WS0076)

摘　　要：目的研究缺氧诱导因子-1α(HIF-1α)和程序性死亡因子配体1(PD-L1)在肺腺癌中的表达与临床病理特征的关系,探讨肺腺癌中HIF-1α对PD-L1的调控作用。方法应用免疫组织化学方法检测99例肺腺癌组织中HIF-1α、PD-L1的表达。Co Cl2模拟化学性缺氧处理肺腺癌细胞,并将其分为正常组及CoCl_2组,qRT-PCR检测HIF-1α、PD-L1 mRNA表达,Western blotting检测HIF-1α、PD-L1蛋白表达。siRNA-HIF-1α瞬时转染肺腺癌细胞,并将其分为阴性对照组及siR-HIF-1α组,qRT-PCR、Western blotting检测转染效率及PD-L1 mRNA和蛋白的表达。结果 99例肺腺癌组织中,HIF-1α和PD-L1的阳性率分别为47.48%和34.34%,HIF-1α表达水平与患者年龄和临床分期有关(P<0.05),PD-L1表达水平与患者临床分期有关(P<0.05),HIF-1α蛋白表达与PD-L1蛋白表达呈正相关(P<0.01)。与正常组相比,CoCl_2组细胞中HIF-1α蛋白表达水平明显升高(t=-2.394,P=0.029),PD-L1 mRNA及蛋白表达水平随之明显升高(t=-3.146,P=0.006;t=-3.308,P=0.004)。与阴性对照组相比,siR-HIF-1α组沉默处理细胞后,PD-L1 mRNA及蛋白表达水平显著降低(t=2.746,P=0.014;t=2.339,P=0.033)。结论肺腺癌组织中HIF-1α和PD-L1明显共表达;PD-L1表达受HIF-1α调控。Objective To analyze the association of hypoxia-inducible factor-1α （HIF-1α） and programmed death lig- and 1 （PD-L1） expression and clinicopathologic features in lung adenocarcinoma, and to investigate the potential role of HIF-1 ct in the regulation of PD-L1 expression. Methods The expressions of HIF-1α and PD-L1 of 99 cases with lung adenocarcinoma were examined by immunohistochemical method. The lung adenocarcinoma cells were treated with hy- poxia mimic CoC12 and divided into normal group and CoC12 group. The mRNA and protein expressions of HIF-1α and PD-L1 were detected with qRT-PCR and Western blotting, respectively. The lung adenocarcinoma cells were transfect- ed with siRNA-HIF-1α and divided into negative control group and siR-HIF-1α group. The transfection efficiency of siRNAs and the expression of PD-L1 were detected by qRT-PCR and Western blotting, respectively. Results The pos- itive expression rates of HIF-1α and PD-L1 were 47.48% and 34.34% in 99 cases with lung adenocarcinoma, respec-tively. The expression of HIF-1α was correlated with age and clinical stage （ P 〈 0.05 ）. The expression of PD-L1 was correlated with clinical stage （P 〈 0.05 ）. The expressions of HIF-1α and PD-L1 were positive correlated （P 〈 0.01 ）. Compared with the normal group, the protein expression of HIF-1α significantly increased （ t = - 2. 394, P = 0. 029 ）, and the mRNA and protein expressions of PD-L1 increased subsequently in the CoCI2 group （ t = - 3. 146, P = 0. 006 ; t = - 3. 308, P = 0. 004）. Compared with the negative control group, the mRNA and protein expressions of PD-L1 decreased dramatically in the siR-HIF-1α group （ t = 2. 746, P = 0. 014 ; t = 2. 339, P = 0. 033 ）. Conelusion The HIF-1α and PD-L1 proteins are highly co-expressed, and HIF-1α can up-regulate the expression of PD-LI in lung ade- nocarcinoma.

关 键 词：缺氧诱导因子-1Α 程序性死亡因子配体1 肺腺癌 

分 类 号：R734.2[医药卫生—肿瘤]