细胞因子与肝癌关系的巢式病例对照研究

A nested case-control study on the relationship between cytokine and hepatocellular carcinoma

目的探索导致HBV基本核心启动子(BCP)双突变(A1762T,G1764A)株相关肝癌患者免疫压力降低的细胞因子,及其与肝癌之间的关系。方法按照巢式病例对照研究原理,从隆安县研究队列中选择同为感染HBV BCP双突变株者作为研究对象,其中的肝癌患者纳入病例组、HBsAg无症状携带者纳入对照组。采用流式免疫荧光法先后检测2004年和2019年所采集的研究对象血清中,已知被HBV诱导改变的免疫细胞所分泌的10个细胞因子,包括IL-1β、IL-2、IL-4、TNF-α、IL-6、IL-10、IL-17A、IL-12、IFN-γ和IL-13;采用Mann-WhitneyU检验对数据进行统计分析。结果研究对象包括肝癌患者9例(病例组)、HBsAg无症状携带者10例(对照组)。2004年只有细胞因子IL-10的表达量在病例组和对照组间差异有统计学意义(Z=-2.167,P=0.030),IL-10在病例组和对照组的表达量分别为(4.718±2.075)pg/mL和(2.899±0.745)pg/mL。2019年病例组细胞因子IL-6、IL-10和IL-12的表达量均高于对照组(P值分别为0.041、0.020和0.003)。对于病例组,细胞因子IL-10在2019年的表达量[(11.433±7.242)pg/mL]高于2004年[(4.718±2.075)pg/mL],差异有统计学意义(Z=-2.693,P=0.007)。结论细胞因子IL-6、IL-10和IL-12与HBV BCP双突变株携带者发生肝癌有关;细胞因子IL-10表达量升高与HBV BCP双突变(A1762T,G1764A)株相关肝癌患者机体免疫压力降低有关。

Objective To explore the cytokines led to reduced immune pressure in patients with liver cancer associated with HBV basic core promoter(BCP)double mutation(A1762T,G1764A)strains,and their relationship with liver cancer.Methods Subjects infected with HBV BCP double mutant strains were selected from the Long’an county research cohort as research subjects,according to the principle of nested casecontrol study.Among them,liver cancer patients were included in the case group,and HBsAg asymptomatic carriers were included in the control group.10cytokines secreted by immune cells known to be induced by HBV in the sera of the subjects collected in 2004and 2019,including IL-1β,IL-2,IL-4,TNF-α,IL-6,IL-10,IL-17A,IL-12,IFN-γ,and IL-13,were detected using Flow immunofluorescence.The data were statistically analyzed by Mann-Whitney U test.Results The study subjects include 9 patients with liver cancer(case group)and 10 asymptomatic HBsAg carriers(control group).In 2004,only the expression level of cytokine IL-10 was significantly different between case and control(Z=-2.167,P=0.030).The expression level of IL-10 in case group and control group were(4.718±2.075)pg/mL and(2.899±0.745)pg/mL,respectively.In 2019,the expression levels of cytokines IL-6,IL-10,and IL-12 in the case group were significantly higher than in control group(their P values were 0.041,0.020,and 0.003,respectively).In case group,the expression level of IL-10 in 2019(11.433±7.242)pg/mL was significantly higher than that in 2004(4.718±2.075)pg/mL,and the difference was statistically significant(Z=-2.693,P=0.007).Conclusions Cytokines IL-6,IL-10 and IL-12 are associated with liver cancer in HBV BCP double mutant carriers.The increased expression of cytokine IL-10 is associated with reduced immune pressure in patients with liver cancer associated with HBV BCP double mutation(A1762T,G1764A)strains.