B7-H1及其受体PD-1分子在原发性肝癌组织中的表达及临床意义

Expression and clinical significance of B7-H1 and PD-1 in primary hepatocellular carcinoma tissues

目的:分析B7-H1和PD-1分子在原发性肝癌组织中的表达,并探讨其在肝癌发生过程中的临床意义.方法:采用免疫组织化学染色和半定量逆转录聚合酶链反应(RT-PCR)检测42例原发性肝癌组织及对应的癌旁正常肝组织中B7-H1蛋白和mRNA表达,分析B7-H1分子与肝癌分化程度、有无侵袭转移的关系.分离肝组织内淋巴细胞,流式细胞仪分析PD-1分子在T细胞表面表达,以及B7-H1信号对肝癌组织内T细胞功能的影响.结果:原发性肝癌组织中B7-H1蛋白及mRNA表达水平均比癌旁组织和正常组织显著升高(85.71%vs28.57%,7.14%;0.73±0.21vs0.35±0.12,0.23±0.07,均P<0.05),B7-H1阳性细胞与癌组织分化程度、有无侵袭转移相关(χ2=7.876,8.492,均P<0.05),但与患者性别、年龄、肿瘤大小、肿块类型及AFP水平无相关关系.肝癌组织中T细胞表达PD-1水平比癌旁对照显著上高(20.15%±3.47%vs2.67%±0.53%,P<0.001).结论:肝癌中B7-H1分子表达可能抑制肝癌组织内T细胞功能,促进肝癌细胞逃避免疫监控,阻断肝癌细胞表面B7-H1/PD-1信号传导,可能成为肝癌免疫治疗的新途径.

AIM： To analyze expression of B7-H1 and PD-1 in primary hepatocelluar carcinoma （HCC） tissues and to investigate its role in HCC carcinogenesis. METHODS： B7-H1 protein expression in HCC and normal liver tissues was determined using immunohistochemistry assay and real-time PCR （RT-PCR） in 42 patients. PD-1 expression in in-trahepatic lymphocytes was detected using flow cytometry. The relationship between B7-H1 and the Edmondson grading and tumor metastasis of HCC were analyzed subsequently. RESULTS： The B7-H1 protein and mRNA lev-els were significantly increased in HCC tissues compared with normal liver tissues （85.71% vs 28.57%, 7.14%; 0.73 ± 0.21 vs 0.35 ± 0.12, 0.23 ± 0.07, all P 〈 0.05）. The expression of B7-H1 pro-tein mRNA in HCC was not correlated to the gender of patients, age, tumor size, tissue type groups and α-fetoprotein expression, but signifi-cantly correlated to the Edmondson grading and tumor metastasis （χ2 = 7.876, 8.492, both P 〈 0.05）. PD-1 was also highly expressed in T cells from HCC tissues than that in controls （20.15% ± 3.47% vs 2.67% ± 0.53%, P 〈 0.001）. CONCLUSION： B7-H1 is highly expressed in HCC tissues, and the expression of B7-H1 can reflect the HCC infiltration. Therefore, blockade of B7-H1 signaling pathway may have a thera-peutic role in HCC treatment.