CD8^+T PD-1在HBV感染临床转归中的意义及诊断价值的探讨

The Significance of PD-1 in the Clinical Outcome of HBV Infection and the Value of Hepatocellular Carcinoma Assisted Diagnosis

目的探讨外周血中CD8^+T淋巴细胞(CD8^+Tlymphocytes cell)上程序性死亡因子-1(Programmed death-1,PD-1)在HBV感染后不同临床转归患者中表达的变化趋势及其对肝癌辅助诊断的价值。方法收集健康人16例、CHB37例、LC32例、HCC32例患者外周血样本。分别应用流式细胞术、荧光定量PCR、血清生化检测CD8^+TPD-1、HBVDNA、常见的肝功能生化指标,收集患者AFP临床数据。分析CD8^+TPD-1在HBV感染后迁移变化中的表达情况,分析其与HBVDNA、ALT、AST、ALB等指标的相关性,与AFP比较分析其辅助诊断肝癌的临床价值。结果正常、CHB、LC、HCC组CD8^+T细胞PD-1(%)分别为:5.30±1.06、15.51±18.57、20.87±39.75和24.24±20.80。HBV感染患者CD8+T细胞PD-1表达水平明显高于正常组(P<0.05)。CD8^+TPD-1的表达水平在CHB组与LC组间无明显差异(P>0.05),HCC组CD8^+TPD-1的表达水平显著高于CHB、LC组(P<0.05)。CD8^+TPD-1水平与ALT、AST、HBVDNA载量没有明显相关性(P>0.05),与ALB水平呈负相关(r=-0.241,P=0.009)。CD8^+T细胞PD-1ROC曲线下面积AUC=0.773大于AFPROC曲线下面积AUC=0.603差异有统计学意义(P<0.05)。结论CD8^+TPD-1在CHB、LC、HCC患者外周血中表达水平逐渐升高,是HBV感染恶化的标志,可用于肝癌辅助诊断及预后评估。

Objective To study CD8^+ T lymphocytes cells expressed programmed death-1 (PD-1) in peripheral boold of patients with HBV infection and its value in the diagnosis of hepatocellular carcinoma.Methods Blood samples were collected from healthy subjects(16 healthy people),CHB(37 patients),LC (32 patients)and HCC (32 patients).The expression of PD-1 in CD8^+ T cells was detected by flow cytometry.The serum HBV DNA loading was measured by fluorescence quantitative PCR.The data of AFP were collected in clinical and the serum ALT,AST and ALB were measured by biochemical test.The relationship between CD8^+ T cell PD-1 expression in liver disease,and the correlation between HBV DNA load,ALT,AST and ALB were analyzed.Evaluate the value of diagnosis on CD8^+T PD-1 comparing with AFP.Results The PD-1 (%) of CHB,LC and HCC groups were 5.30 ± 1.06,15.51 ± 18.57,20.87±39.75 and 24.24 ± 20.80,respectively.The expression of PD-1 in CD8^+ T cells was significantly higher than that in normal controls ( P < 0.05 ).There was no significant difference in the expression level of CD8^+T PD-1 between CHB and LC group ( P > 0.05).The expression of CD8^+T PD-1 in HCC group was significantly higher than that in CHB and LC group ( P <0.05).There was no significant correlation between the level of CD8^+T PD-1 and ALT,AST,HBV DNA (P> 0.05),and negatively correlated with ALB level ( r =-0.241,P =0.009).The area under the ROC curve of CD8^+T PD-1=0.773 was significantly higher than that of AFP = 0.603 ( P <0.05).Conclusion The expression of CD8^+T PD-1 in peripheral blood of CHB,LC and HCC patients is gradually increased,which proves that HBV infection is related to the exhaustion of T cell function caused by PD-1 overexpression.CD8^+T PD-1 may be useful for the diagnosis and prognosis of hepatocellular carcinoma.