共刺激分子B7-H3在人原发性肝癌中的表达及临床意义

Expression and clinical significance of costimulatory molecule B7-H3 in human hepatocellular carcinoma

背景与目的:B7-H3是近年来新发现的协同刺激分子B7家族成员,但目前其在人原发性肝癌中的表达及作用尚不明确。本研究旨在通过检测人肝癌组织中B7-H3分子的表达,探讨B7-H3在肝癌发生、发展中的临床意义。方法:采用免疫组织化学法、半定量逆转录聚合酶链式反应(reverse transcription PCR,RT-PCR)检测71例肝癌组织、对应癌旁组织及正常肝组织中B7-H3分子的蛋白、mRNA表达以及CD8+T淋巴细胞的浸润程度。结果:肝癌组织中B7-H3蛋白的阳性表达率为93.0%(68/71),而B7-H3在癌旁及正常肝组织中几乎不表达。肝癌组织中B7-H3 mRNA表达水平比癌旁组织和正常肝组织显著升高(P<0.05)。B7-H3的表达与患者AFP水平、TNM分期及肝内有无转移差异有统计学意义(P<0.05),与肿瘤组织中CD8+T淋巴细胞浸润程度呈负相关(P<0.05),与患者预后呈负相关(P<0.05)。结论:B7-H3在肝癌中高表达,和多项临床病理因素具有明显的关联。肝癌中B7-H3分子表达可能参与了抑制肝癌组织内CD8+T细胞功能,促进肝癌细胞逃避免疫监视,提示B7-H3在肝癌早期诊断、判断预后及靶向治疗中具有潜在的临床应用价值。

Background and purpose： B7-H3 is a newly identified costimulatory family member, however, its exact role in human hepatocellular carcinoma （HCC） is still unknown. In the present study, we analyzed the expression of B7-H3 in HCC tissues and investigated its potential clinical role in HCC carcinogenesis. Methods： The expression of B7-H3 and the intensity of tumor infiltrating CD8＋T lymphocytes in 71 surgically resected specimens, corresponding adjacent and normal liver tissues of HCC were evaluated by immunohistochemistry and reverse transcription-polymerase chain reaction （RT-PCR）. Results： In these tumor specimens, 93.0% （68/71） samples were positive for B7-H3, while was almost negative in adjacent tissues and normal liver tissues. The B7-H3 mRNA level was also significantly increased in HCC tissues compared with adjacent and normal liver tissues （P〈0.05）. The abnormal expression of B7-H3 was correlated with the level ofAFP, TNM stage and the state of intrahepatic metastasis （P〈0.05）. Meanwhile, the expression of B7-H3 in cancer cells was negatively correlated with the intensity of tumor infiltrating CD8＋T lymphocytes （P〈0.05） and postoperative prognosis （P〈0.05）. Conclusion： B7-H3 is overexpressed in the tissues of HCC, and B7-H3 expression is highly correlated with several clinical parameters. Moreover, overexpression of B7-H3 in HCC tissues can reflect CDS＋T cell infiltration and may help tumor cells avoid immune surveillance. Therefore, B7-H3 plays important roles in early prediction, diagnosis and survival of HCC. Blockade of B7-H3 signaling pathway may have a therapeutic role in HCC treatment.