PD-1、CTLA-4、Th1/Th2及其相关细胞因子在原发性肝癌患者外周血中的表达及与肿瘤标志物的相关性  

Study on the expression of PD-1,CTLA-4,Th1/Th2,and related cytokines in peripheral blood of patients with primary liver cancer and their correlation with tumor markers

作　　者：陈永霞 李琦[1] 刘春梅 CHEN Yong-xia;LI Qi;LIU Chun-mei(Jianyang Hospital of Traditional Chinese Medicine,Chengdu 641400,Sichuan,China)

机构地区：[1]简阳市中医医院检验科,四川成都641400

出　　处：《广东医学》2025年第2期176-180,共5页Guangdong Medical Journal

摘　　要：目的探索肝细胞癌(HCC)患者外周血程序性细胞死亡受体1(programmed death-1,PD-1)、细胞毒T淋巴细胞相关抗原4(cytotoxic T lymphocyte-associated antigen-4,CTLA-4)、Th1/Th2及其相关细胞因子水平,并分析其与肿瘤标志物甲胎蛋白(alpha fetoprotein,AFP)、异常凝血酶原(protein induced by vitamin K absence or antagonistⅡ,PIVKAⅡ)的相关性。方法选择2021年1月至2022年12月简阳市中医医院收治的50例HCC患者作为HCC组,选择同期行健康体检者作为对照组。采用酶联免疫吸附法测定测定外周血AFP、PIVKAⅡ、CTLA-4、PD-1、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、γ干扰素(interferonγ,IFN-γ)、白细胞介素-6(interleukin-6,IL-6)和白细胞介素-10(interleukin-10,IL-10)的水平。采用酶联免疫斑点法测定外周血Th1/Th2。比较两组患者上述指标差异,并采用Pearson法将上述指标与HCC组患者AFP和PIVKAⅡ水平进行相关性分析。结果与对照组相比,HCC组患者外周血TNF-α、IFN-γ及Th1/Th2细胞比例明显下降,而AFP、PIVKAⅡ、IL-6、IL-10、CTLA-4和PD-1水平则明显升高,差异有统计学意义(P<0.05)。相关性分析表明,Th1/Th2与AFP和PIVKA负相关性最高,而PD-1与AFP和PIVKA正相关性最高(r>|7|,P<0.05)。结论HCC患者外周血Th1/Th2明显降低,而CTLA-4和PD-1显著升高,且与HCC血清肿瘤标志物AFP和PIVKA具有密切关系,基于上述指标可为HCC的临床诊断和免疫治疗评估提供参考依据。Objective To investigate the levels of programmed death-1(PD-1),cytotoxic T lymphocyte-associated antigen-4(CTLA-4),Th1/Th2,and related cytokines in the peripheral blood of patients with hepatocellular carcinoma(HCC)and analyze their correlation with tumor markers alpha fetoprotein(AFP)and protein induced by vitamin K absence or antagonistⅡ(PIVKA-Ⅱ).Methods Fifty HCC patients treated at Jianyang Hospital of Traditional Chinese Medicine from January 2021 to December 2022 were selected as the HCC group.A control group was composed of individuals undergoing health check-ups at the same time.Levels of peripheral blood AFP,PIVKA-Ⅱ,CTLA-4,PD-1,tumor necrosis factor-α(TNF-α),interferonγ(IFN-γ),interleukin-6(IL-6),and interleukin-10(IL-10)were measured using enzyme-linked immunosorbent assay(ELISA).The Th1/Th2 cell ratio was determined by enzyme-linked immunospot assay.Differences between the two groups for the above indicators were compared,and Pearson correlation analysis was performed to assess the relationship between these indicators and the levels of AFP and PIVKA-Ⅱin the HCC group.Results Compared to the control group,the HCC group showed significant decreases in peripheral blood levels of TNF-α,IFN-γ,and the Th1/Th2 cell ratio.In contrast,levels of AFP,PIVKA-Ⅱ,IL-6,IL-10,CTLA-4,and PD-1 were significantly increased(P<0.05).Correlation analysis revealed that Th1/Th2 showed the highest negative correlation with AFP and PIVKA-Ⅱ,while PD-1 exhibited the highest positive correlation with these markers(|r|>7,P<0.05).Conclusion In HCC patients,peripheral blood Th1/Th2 levels are significantly decreased,while CTLA-4 and PD-1 levels are markedly increased,closely correlating with serum tumor markers AFP and PIVKA-Ⅱ.These indicators may provide valuable references for clinical diagnosis and assessment of immunotherapy in HCC.

关 键 词：原发性肝癌 程序性细胞死亡受体1 细胞毒T淋巴细胞相关抗原4 辅助性T细胞 

分 类 号：R735.7[医药卫生—肿瘤] R392[医药卫生—临床医学]