HBV相关原发性肝癌患者循环血miR-155水平与相关免疫细胞因子、HBV-DNA载量的关系及意义

CORRELATION OF PLASMA MIR-155 WITH RELATED IMMUNE CYTOKINES AND HBV DNA LOAD IN PATIENTS WITH HBV-RELATED PRIMARY HEPATIC CARCINOMA AND ITS CLINICAL SIGNIFICANCE

目的探讨乙型肝炎病毒(HBV)相关原发性肝癌(PHC)患者循环血miR-155水平与相关免疫细胞因子、HBV-DNA载量的关系及临床意义。方法收集2019年1月—2020年3月我院180例HBV感染者的血样,其中包括HBV相关PHC患者(PHC组)75例,乙型肝炎肝硬化患者(HBV-LC组)45例,慢性乙型肝炎患者(CHB组)30例,无症状慢性HBV携带者(HBV组)30例,同时收集健康人群血样50例。分别检测所有受检者血浆中miR-155表达水平及血清中Th1类细胞因子[白细胞介素-12(IL-12)、干扰素-γ(IFN-γ)、肿瘤坏死因子α(TNF-α)]和Th2类细胞因子(IL-4、IL-6、IL-10)的水平。绘制受试者工作特征(ROC)曲线,并计算曲线下面积(AUC),得出miR-155诊断HBV相关PHC的灵敏度和特异度。结果PHC组患者血浆中miR-155水平明显高于其他组(F=9.147,P<0.01),且血浆中miR-155水平与血清中IL-4、IL-6、IL-10水平和HBV-DNA载量、甲胎蛋白水平均呈正相关(r=0.285~0.714,P<0.05),与血清中IL-12、IFN-γ呈负相关(r=-0.595、-0.478,P<0.05)。PHC患者肝功能越差、肿瘤分化程度越高、肿瘤直径越大,血浆中miR-155表达水平越高(t=3.218~5.187,P<0.05)。ROC曲线分析显示,血浆中miR-155对HBV相关性PHC诊断的灵敏度为94.5%,特异度为68.5%,AUC为0.892(95%CI=0.810~0.942)。结论miR-155在HBV相关性PHC患者血液中表达量升高,并且与HBV-DNA载量以及Th1/Th2免疫失衡密切相关,miR-155的检测对临床HBV相关PHC的早期诊断和筛查具有一定的价值。

Objective To investigate the correlation of plasma miR-155 with related immune cytokines and HBV DNA load in patients with HBV-related primary hepatic carcinoma(PHC)and its clinical significance.Methods Blood samples were collected from 180 patients with HBV infection who were treated in our hospital from January 2019 to March 2020,among whom 75 had HBV-related PHC(PHC group),45 had hepatitis B cirrhosis(HBV-LC group),30 had chronic hepatitis B(CHB group),and 30 were asymptomatic chronic HBV carriers(HBV group),and blood samples were also collected from 50 healthy individuals.The expression level of miR-155 in plasma and the serum levels of Th1 cytokines[interleukin-12(IL-12),interferon gamma(IFN-γ),and tumor necrosis factor-α(TNF-α)]and Th2 cytokines(IL-4,IL-6,and IL-10)were measured for all subjects.The receiver operating characteristic(ROC)curve was plotted and the area under the ROC curve(AUC)was calculated to obtain the sensitivity and specificity of miR-155 in the diagnosis of HBV-related PHC.Results The PHC group had a significantly higher plasma level of miR-155 than the other groups(F=9.147,P<0.01);the plasma level of miR-155 was positively correlated with the serum levels of IL-4,IL-6,and IL-10,HBV DNA load,and alpha-fetoprotein level(r=0.285-0.714,P<0.05)and was negatively correlated with the serum levels of IL-12 and IFN-γ(r=-0.595,-0.478,P<0.05).The PHC patients with poorer liver function,higher degree of tumor differentiation,and larger tumor diameter tended to have a higher expression level of miR-155 in plasma(t=3.218-5.187,P<0.05).The ROC curve analysis showed that plasma miR-155 had a sensitivity of 94.5%,a specificity of 68.5%,and an AUC of 0.892(95%CI=0.810-0.942)in the diagnosis of HBV-related PHC.Conclusion There is an increase in the expression of miR-155 in blood of patients with HBV-related PHC,which is closely associated with HBV DNA load and Th1/Th2 imbalance.Measurement of miR-155 has a certain value in the early diagnosis and screening of HBV-related PHC in clinical practice.