Glypican-3表达影响临床肝癌患者免疫治疗效果的研究  

Study on the effect of glypican-3 expression on immunotherapy in liver cancer patients

作　　者：张雨欣 王静[2] 徐岩[2] 孟子鹤 杨鹏辉 孙计桃 ZHANG Yuxin;WANG Jing;XU Yan;MENG Zihe;YANG Penghui;SUN Jitao(School of Basic Medicine,Inner Mongolia Medical University,Hohhot 010110,China;Institute of Hepato-Pancreato-Biliary Surgery,First Medical Center,Chinese PLA General Hospital,Beijing 100853,China)

机构地区：[1]内蒙古医科大学基础医学院,呼和浩特010110 [2]解放军总医院第一医学中心肝胆胰外科医学部,北京100853

出　　处：《免疫学杂志》2024年第10期773-780,共8页Immunological Journal

基　　金：北京市科技新星计划(20230484472)。

摘　　要：目的探究磷脂酰肌醇蛋白聚糖3(glypican-3,GPC3)表达水平与临床肝癌患者免疫治疗响应的相关性。方法收集解放军总医院2019年1月至2023年5月232例肝癌免疫治疗响应组/耐受组患者的临床资料,统计分析GPC3表达水平与肝癌患者免疫治疗效果的相关性;TCGA数据库验证肝癌患者GPC3高、低表达组中免疫细胞浸润情况;进一步通过实时荧光定量PCR(qPCR)、免疫组化染色方法分别检测肝癌免疫治疗响应组/耐受组患者癌、癌旁配对组织中GPC3表达及免疫细胞浸润情况,并应用多色免疫荧光检测GPC3及相关分子表达。结果临床数据表明肝癌患者GPC3阳性组免疫治疗响应率低,单因素/多因素分析结果表明GPC3是肝癌免疫治疗后肿瘤复发的独立危险因素;TCGA数据库分析结果发现肝癌组织中GPC3高表达导致调节性T细胞(Tregs)浸润增多;肝癌患者癌、癌旁配对组织检测发现GPC3高表达组的免疫治疗效果更差,且Tregs细胞浸润增加,与数据库分析结果一致。TCGA数据库分析结果发现GPC3与CCL20及其配体CCR6均呈正相关,多色免疫组化结果与数据库分析结果一致。结论GPC3在肝癌患者肿瘤组织中高表达,与肝癌免疫治疗耐受呈正相关,GPC3通过CCL20-CCR6信号轴调控Tregs细胞浸润,有望作为预测临床肝癌患者免疫治疗效果的生物标志物。Objective To investigate the correlation between the expression level of glypican-3(GPC3)and the immune therapy response in clinical liver cancer patients.Methods Clinical data of 232 liver cancer immunotherapy response/tolerance group patients from January 2019 to May 2023 at the General Hospital of the People's Liberation Army were collected,and the correlation between GPC3 expression levels and the efficacy of immunotherapy in liver cancer patients was statistically analyzed;TCGA database validation of immune cell infiltration in GPC3 high and low expression groups of liver cancer patients;Further,real-time fluorescence quantitative PCR(qPCR)and immunohistochemical staining methods were used to detect the expression of GPC3 and immune cell infiltration in paired tissues of liver cancer immunotherapy response/tolerance group patients,and multi-color immunofluorescence was applied to detect the expression of GPC3 and related molecules.Results Clinical evidence shows that the GPC3 positive group of liver cancer patients has a low response rate to immunotherapy.Univariate/multivariate analysis results indicate that GPC3 is an independent risk factor for tumor recurrence after liver cancer immunotherapy;The analysis of the TCGA database revealed that high expression of GPC3 in liver cancer tissue leads to increased infiltration of regulatory T cells(Tregs);Paired tissue testing of liver cancer patients and adjacent tissues revealed that the immunotherapy effect was worse in the GPC3 high expression group,and Tregs cell infiltration increased,consistent with the results of database analysis.The TCGA database analysis results showed that GPC3 was positively correlated with CCL20 and its ligand CCR6,and the multi-color immunohistochemistry results were consistent with the database analysis results.Conclusion GPC3 is highly expressed in tumor tissues of liver cancer patients and is positively correlated with immune therapy tolerance in liver cancer.GPC3 regulates Tregs cell infiltration through the CCL20-CCR6 signaling

关 键 词：磷脂酰肌醇蛋白聚糖3 肝癌 免疫治疗 程序性死亡受体1 调节性T细胞 

分 类 号：R735.7[医药卫生—肿瘤]