免疫检查点HHLA2和PD-L1在肝癌组织中的表达及临床意义  

Expression and clinical significance of immune checkpoint molecules HHLA2 and PD-L1 in hepatocellular carcinoma

作　　者：杨静文 唐小童 郭辉 朱悦 张甜甜 刘杨[1,2] 吴穷 汪蕊[1,2] YANG Jing-wen;TANG Xiao-tong;GUO Hui;ZHU Yue;ZHANG Tian-tian;LIU Yang;WU Qiong;WANG Rui(Department of Medical Oncology,The First Affiliated Hospital of Bengbu Medical College,Bengbu Anhui 233004,China;Anhui Province Key Laboratory of Translational Cancer Research,The First Affiliated Hospital of Bengbu Medical College,Bengbu Anhui 233004,China)

机构地区：[1]蚌埠医学院第一附属医院肿瘤内科,安徽蚌埠233004 [2]蚌埠医学院第一附属医院安徽省癌症转化实验室,安徽蚌埠233004

出　　处：《蚌埠医学院学报》2021年第4期425-430,共6页Journal of Bengbu Medical College

基　　金：安徽省高校优秀人才计划项目(gxyqZD2017065);蚌埠医学院第一附属医院杰出青年基金项目(2019byyfyjq03);蚌埠医学院研究生科研创新计划项目(Byycxz1814)。

摘　　要：目的:考察免疫检查点人内源性逆转录病毒-H长端重复相关蛋白2(human endogenous retrovirus-H long terminal repeat-associating protein 2,HHLA2)和程序性死亡配体-1(programmed death ligand-1,PD-L1)在肝细胞癌组织中的表达,分析两者之间表达的相关性及与临床病理特征和临床预后关系。方法:应用免疫组织化学染色方法检测90例肝癌组织及相对应癌旁组织中HHLA2和PD-L1的表达,分析HHLA2和PD-L1在肝癌组织中表达的相关性,并分析HHLA2和PD-L1的表达与肝癌的临床分期、血清甲胎蛋白(AFP)水平、病理分级、慢性乙型肝炎病毒感染、血管侵犯等临床病理参数和总生存时间(OS)之间的关系。结果:在肝癌组织中,HHLA2阳性表达率(49/90,54.4%)高于癌旁组织(33/90,36.7%),但差异无统计学意义(P>0.05);PD-L1阳性表达率(52/90,57.7%)较癌旁组织(44/90,48.9%)差异无统计学意义(P>0.05)。HHLA2与PD-L1表达在肝癌组织中呈正相关关系(r=0.280,P<0.05)。HHLA2在肝癌组织中的表达与肝癌病人年龄、性别、病理分级、血清AFP水平、血管侵犯无关,与临床分期、慢性乙型肝炎病毒感染有关(P<0.05)。PD-L1的表达与肝癌病人年龄、性别、血清AFP水平、血管侵犯、慢性乙型肝炎病毒感染无关,与临床分期和病理分级有关(P<0.05)。HHLA2与PD-L1阳性表达的肝癌病人中位OS同阴性表达病人比较差异无统计学意义(P>0.05)。结论:免疫检查点分子HHLA2与PD-L1在肝癌组织表达有升高趋势,两者之间表达呈正相关关系,HHLA2和PD-L1的表达状态与临床预后无关。HHLA2作为新型免疫检查点分子能否成为晚期肝癌未来潜在的治疗靶点仍需进一步探索研究。Objective:To explore the expression levels of immune checkpoint molecules human endogenous retrovirus-H long terminal repeat-associating protein 2(HHLA2)and programmed death ligand-1(PD-L1)in hepatocellular carcinoma(HCC)tissues,and analyze the correlation between HHLA2 and PD-L1 expression,and relationship between HHLA2 and PD-L1 expression,and clinicalpathological characteristics and prognosis.Methods:The expression levels of HHLA2 and PD-L1 in 90 human HCC tissues and corresponding adjacent tissues were detected using immunohistochemical staining.The correlation between the expression of HHLA2 and PD-L1 in HCC tissues was assessed.The relationship between the expression levels of HHLA2 and PD-L1,and clinical stage,serumα-fetoprotein(AFP)level,pathological grade,chronic hepatitis B virus infection,vascular invasion and over survival time(OS)were analyzed.Results:The positive rates of HHLA2 in HCC tissues and adjacent tissues were 54.4%and 36.7%,respectively,and the difference of which was not statistically significant(P>0.05).The positive rates of PD-L1 in HCC tissues and adjacent tissues were 57.7%and 48.9%,respectively,and the difference of which was not statistically significant(P>0.05).The HHLA2 expression in HCC tissues was positively correlated with PD-L1 expression(r=0.280,P<0.05).The expression of HHLA2 in HCC tissues was not related to the age,sex,pathological grade,serum AFP level and vascular invasion,but related to the clinical stage and chronic hepatitis B virus infection(P<0.05).The expression of PD-L1 in patients with HCC was not associated with the age,sex,serum AFP level,vascular invasion and chronic hepatitis B virus infection,but associated with the clinical stage and pathological grade(P<0.05).There was no statistical significance in OS between positive and negative HHLA2 and PD-L1 expression HCC patients(P>0.05).Conclusions:The expression levels of immune checkpoint molecules HHLA2 and PD-L1 in HCC tissues are on an upward trend,the expression of the two is positively correlated,and the ex

关 键 词：肝肿瘤 免疫检查点 人内源性逆转录病毒-H长端重复相关蛋白2 程序性死亡配体-1 

分 类 号：R735.2[医药卫生—肿瘤]