免疫检查点HHLA2和PD-L1在肝癌组织中的表达及临床意义

杨静文; 唐小童; 郭辉; 朱悦; 张甜甜; 刘杨; 吴穷; 汪蕊

doi:10.13898/j.cnki.issn.1000-2200.2021.04.002

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

摘要

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。

Abstract:
ObjectiveTo 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.
MethodsThe 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, serum α-fetoprotein(AFP) level, pathological grade, chronic hepatitis B virus infection, vascular invasion and over survival time(OS) were analyzed.
ResultsThe 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).
ConclusionsThe 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 expressions of HHLA2 and PD-L1 are not related to the prognosis of HCC patients.HHLA2, as a new immune checkpoint molecule, may be a potential therapeutic target for advanced liver cancer in the future, which still needs to be further studied.

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