PD-1、PD-L1、CA125在原发性肝癌中的表达变化及临床意义
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摘要
目的探讨程序性死亡受体-1(programmed death receptor-1,PD-1)、程序性死亡配体-1(programmed death receptor ligand-1,PD-L1)、癌胚抗原125(carcinoembryonic antigen 125,CA125)在原发性肝癌中的表达变化及临床意义。方法选取2016年3月至2018年3月在我院就诊的原发性肝癌患者70例作为研究对象。取所有患者手术切除癌组织标本以及与距离癌组织5 cm以上的癌旁正常肝组织,进行连续切片作免疫组化标记以及革兰染色待用。酶联免疫吸附测定PD-1、PD-L1、CA125表达,免疫组化染色处理后进行结果判定。结果原发性肝癌组织CA125、PD-1、PD-L1阳性表达水平显著高于癌旁组织(P <0. 05)。原发性肝癌组织PD-1、PD-L1、CA125阳性表达与患者TNM分期、肿瘤大小、肿瘤转移、腹水有关。Ⅲ-Ⅳ期、肿瘤> 5cm、有肿瘤转移、有腹水的患者癌组织PD-1、PD-L1、CA125阳性表达率均较高(P <0. 05)。原发性肝癌组织PD-1、PD-L1、CA125两两之间呈正相关(P均<0. 05)。结论 PD-1、PD-L1、CA125表达水平与原发性肝癌具有相关性,PD-1、PD-L1、CA125的异常表达,参与了原发性肝癌的发展,为原发性肝癌的治疗提供一定的理论基础。
Objective To investigate the expression and clinical significance of programmed death receptor-1( PD-1),programmed death ligand-1( PD-L1) and carcinoembryonic antigen 125( CA125) in primary liver cancer. Methods Seventy patients with primary hepatocellular carcinoma treated in our hospital from March 2016 to March 2018 were selected as the study subjects. All patients met the diagnostic criteria of primary liver cancer. All specimens of cancer tissues and normal liver tissues adjacent to the cancer tissues more than 5 cm away from the cancer tissues were taken for immunohistochemical staining and Gram staining. The expressions of PD-1,PD-L1 and CA125 were detected by ELISA,and the results were determined by immunohistochemical staining.Results The positive expression levels of CA125,PD-1 and PD-L1 in cancer tissues were significantly higher than those in adjacent tissues( P < 0. 05). The positive expression of PD-1,PD-L1 and CA125 was related to TNM stage,tumor size,tumor metastasis and ascites in patients with primary hepatocellular carcinoma. The positive expressions of PD-1,PD-L1 and CA125 were higher in patients with ascites( P < 0. 05). There was a positive correlation between PD-1 and PD-L1,between PD-1 and CA125,and between PD-L1 and CEA125. Conclusion The expressions of PD-1,PD-L1 and CA125 are correlated with primary hepatocellular carcinoma. The abnormal expressions of PD-1,PD-L1 and CA125 participate in the development of primary hepatocellular carcinoma and provide a theoretical basis for the treatment of primary hepatocellular carcinoma.
Objective To investigate the expression and clinical significance of programmed death receptor-1( PD-1),programmed death ligand-1( PD-L1) and carcinoembryonic antigen 125( CA125) in primary liver cancer. Methods Seventy patients with primary hepatocellular carcinoma treated in our hospital from March 2016 to March 2018 were selected as the study subjects. All patients met the diagnostic criteria of primary liver cancer. All specimens of cancer tissues and normal liver tissues adjacent to the cancer tissues more than 5 cm away from the cancer tissues were taken for immunohistochemical staining and Gram staining. The expressions of PD-1,PD-L1 and CA125 were detected by ELISA,and the results were determined by immunohistochemical staining.Results The positive expression levels of CA125,PD-1 and PD-L1 in cancer tissues were significantly higher than those in adjacent tissues( P < 0. 05). The positive expression of PD-1,PD-L1 and CA125 was related to TNM stage,tumor size,tumor metastasis and ascites in patients with primary hepatocellular carcinoma. The positive expressions of PD-1,PD-L1 and CA125 were higher in patients with ascites( P < 0. 05). There was a positive correlation between PD-1 and PD-L1,between PD-1 and CA125,and between PD-L1 and CEA125. Conclusion The expressions of PD-1,PD-L1 and CA125 are correlated with primary hepatocellular carcinoma. The abnormal expressions of PD-1,PD-L1 and CA125 participate in the development of primary hepatocellular carcinoma and provide a theoretical basis for the treatment of primary hepatocellular carcinoma.
引文
[1]张明媛，牛俊奇．东方国家原发性肝癌发病趋势及影响因素[J]．临床肝胆病杂志，2018,34(7):1399-1402.
[2]王静，石明伟．甲胎蛋白阴性原发性肝癌诊断进展[J]．医学综述，2016,22(2):269-273.
[3]王曦晖，蒋祖辉，周琼仙，等．血清AFP,CEA,CA125单独或联合检测对原发性肝癌早期诊断的临床价值研究[J]．现代生物医学进展，2017,17(12):2346-2348.
[4]刘伟，杨记康，张增增，等．肝癌患者腹腔积液中可溶性程序性死亡蛋白1(s PD-1)及其配体表达水平[J]．微生物学免疫学进展，2017,45(2):24-28.
[5]刘伟，柴琳，粱军利，等．肝癌患者外周血CD3+T细胞和CD19+B细胞中程序性死亡蛋白1(PD-1)及其配体表达水平增加[J]．细胞与分子免疫学杂志，2016,32(9):1243-1247.
[6]王耿杰，马良赟，沈宇舟，等．PD-1、PD-L1表达与食管癌的临床病理特征及预后的关系[J]．中国实验诊断学，2018,22(10):1751-1753.
[7]王建，严嘉仪．原发性肝癌肉瘤65例分析[J]．中华肝胆外科杂志，2017,23(12):845-847.
[8] Berretta M,Cavaliere C,Alessandrini L,et al. Serum and tissue markers in hepatocellular carcinoma and cholangiocarcinoma:clinical and prognostic implications[J]. Oncotarget,2017,8(8):14192-14220.
[9]鹿存芝，李向阳．甲胎蛋白联合CA199、AFU及CEA在原发性肝癌中的诊断价值[J]．检验医学与临床，2017,14(10):1412-1414.
[10]韩朝辉，张余川，吴清艳．甲胎蛋白、癌胚抗原和糖类抗原199联合检测在原发性肝癌诊断中的应用研究[J]．中国医药导报，2013,10(4):92-93,100.
[11]罗准，崔巍．肝癌分子发病机制中非编码RNA的研究进展[J]．中华肝脏病杂志，2018,26(10):797-800.
[12]柳健，谭诗云，李明，等．原发性肝癌肿瘤标志物的研究进展[J]．医学研究杂志，2016,45(10):12-15,34.
[13]邱志琦，朱嫦琳，詹建清．联合检测PIVKA-Ⅱ、AFP和CA125在肝癌筛查和早期诊断中的临床应用价值[J]．临床检验杂志(电子版)，2018,7(3):408-410.
[14]刘宇静，吴学军．AFP、CA125、CA199联合检测在原发性肝癌诊断中的应用价值[J]．智慧健康，2018,4(3):45-46.
[15]马丽．血清糖类抗原CA-199、CA-125对诊断肺癌、肝癌的临床价值[J]．中国社区医师，2018,34(32):118-119.
[16]郑琼燕．血清AFP CA125 CA153 CA199联合检测对肝癌的诊断意义评价[J]．基层医学论坛，2018,22(10):1395-1397.
[17]廖茹，孙晓非，甄子俊，等．神经母细胞瘤组织中程序性死亡配体1的表达及意义[J]．中华儿科杂志，2018,56(10):735-740.
[18]吴卢侃璇，朱珊，于金习，等．程序性死亡因子-1及其配体-1在子宫腺肌病中的表达及意义[J]．山东大学学报(医学版)，2017,55(10):90-96.
[19]王玲玲，高颖，沈冰，等．肺鳞癌组织PD-L1表达变化及其与患者临床病理参数和预后的关系[J]．山东医药，2017,57(8):25-28.
[20]李夏伊，郑磊贞．程序性死亡蛋白1/程序性死亡配体1抑制剂在晚期胃癌治疗中的应用[J]．上海交通大学学报(医学版)，2018,38(10):1259-1264.
[21]董银萍，李德冠．肿瘤免疫治疗与PD-1/PD-L1抑制剂的研究进展[J]．国际生物医学工程杂志，2018,41(1):72-77.
[22]季沈杰，龚莉．血清AFP、CA125、TK1联合检测对原发性肝癌的诊断价值[J]．热带医学杂志，2018,18(11):1482-1485.
[23]兰福全，李秀云，卢斌．四种肿瘤标志物对肝癌诊断的临床意义[J]．医学信息，2018,31(21):164-166.
[2]王静，石明伟．甲胎蛋白阴性原发性肝癌诊断进展[J]．医学综述，2016,22(2):269-273.
[3]王曦晖，蒋祖辉，周琼仙，等．血清AFP,CEA,CA125单独或联合检测对原发性肝癌早期诊断的临床价值研究[J]．现代生物医学进展，2017,17(12):2346-2348.
[4]刘伟，杨记康，张增增，等．肝癌患者腹腔积液中可溶性程序性死亡蛋白1(s PD-1)及其配体表达水平[J]．微生物学免疫学进展，2017,45(2):24-28.
[5]刘伟，柴琳，粱军利，等．肝癌患者外周血CD3+T细胞和CD19+B细胞中程序性死亡蛋白1(PD-1)及其配体表达水平增加[J]．细胞与分子免疫学杂志，2016,32(9):1243-1247.
[6]王耿杰，马良赟，沈宇舟，等．PD-1、PD-L1表达与食管癌的临床病理特征及预后的关系[J]．中国实验诊断学，2018,22(10):1751-1753.
[7]王建，严嘉仪．原发性肝癌肉瘤65例分析[J]．中华肝胆外科杂志，2017,23(12):845-847.
[8] Berretta M,Cavaliere C,Alessandrini L,et al. Serum and tissue markers in hepatocellular carcinoma and cholangiocarcinoma:clinical and prognostic implications[J]. Oncotarget,2017,8(8):14192-14220.
[9]鹿存芝，李向阳．甲胎蛋白联合CA199、AFU及CEA在原发性肝癌中的诊断价值[J]．检验医学与临床，2017,14(10):1412-1414.
[10]韩朝辉，张余川，吴清艳．甲胎蛋白、癌胚抗原和糖类抗原199联合检测在原发性肝癌诊断中的应用研究[J]．中国医药导报，2013,10(4):92-93,100.
[11]罗准，崔巍．肝癌分子发病机制中非编码RNA的研究进展[J]．中华肝脏病杂志，2018,26(10):797-800.
[12]柳健，谭诗云，李明，等．原发性肝癌肿瘤标志物的研究进展[J]．医学研究杂志，2016,45(10):12-15,34.
[13]邱志琦，朱嫦琳，詹建清．联合检测PIVKA-Ⅱ、AFP和CA125在肝癌筛查和早期诊断中的临床应用价值[J]．临床检验杂志(电子版)，2018,7(3):408-410.
[14]刘宇静，吴学军．AFP、CA125、CA199联合检测在原发性肝癌诊断中的应用价值[J]．智慧健康，2018,4(3):45-46.
[15]马丽．血清糖类抗原CA-199、CA-125对诊断肺癌、肝癌的临床价值[J]．中国社区医师，2018,34(32):118-119.
[16]郑琼燕．血清AFP CA125 CA153 CA199联合检测对肝癌的诊断意义评价[J]．基层医学论坛，2018,22(10):1395-1397.
[17]廖茹，孙晓非，甄子俊，等．神经母细胞瘤组织中程序性死亡配体1的表达及意义[J]．中华儿科杂志，2018,56(10):735-740.
[18]吴卢侃璇，朱珊，于金习，等．程序性死亡因子-1及其配体-1在子宫腺肌病中的表达及意义[J]．山东大学学报(医学版)，2017,55(10):90-96.
[19]王玲玲，高颖，沈冰，等．肺鳞癌组织PD-L1表达变化及其与患者临床病理参数和预后的关系[J]．山东医药，2017,57(8):25-28.
[20]李夏伊，郑磊贞．程序性死亡蛋白1/程序性死亡配体1抑制剂在晚期胃癌治疗中的应用[J]．上海交通大学学报(医学版)，2018,38(10):1259-1264.
[21]董银萍，李德冠．肿瘤免疫治疗与PD-1/PD-L1抑制剂的研究进展[J]．国际生物医学工程杂志，2018,41(1):72-77.
[22]季沈杰，龚莉．血清AFP、CA125、TK1联合检测对原发性肝癌的诊断价值[J]．热带医学杂志，2018,18(11):1482-1485.
[23]兰福全，李秀云，卢斌．四种肿瘤标志物对肝癌诊断的临床意义[J]．医学信息，2018,31(21):164-166.
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