APOBEC3B基因在乙肝相关性肝癌中的作用及机制研究

Hepatocellular carcinomas (HCC) are one of the most commen tumors in the whole world. It has been well known that infection with hepatitis B virus (HBV) is the major etiological factor for the development and recurrence of HCC. Therefore, it is very important to investigate the mechanisms of HBV infection in HCC development and recurrence. APOBEC3B belongs to a family of cytidine deaminases involved in innate cellular immunity against virus including HBV.Recent studies have also documented that A3B are able to edit the HBV genome, raising the possibility that A3B may inhibit HBV infection with interaction with interferon.Our previous studies show A3B deletion is associated with risks of persistent HBV infection and HCC development by genotyping A3B in individuals with HBV related HCC, persistent HBV infection and healthy controls, suggesting that the deletion of A3B attenuates HBV clearance, which in turn may result in persistent HBV infection and increased risk for developing HCC. However, the function and mechanism of A3B in the development and progression of HBV related HCC is still unknown.This program is designed to study the relationship between the expression level of A3B in HCC specimen and prognosis and interferon treament response in HCC patients. Then the relations among A3B, HBV replication, interferon and hepatocellular carcinoma growth will be studied in vitro.

肝细胞肝癌是目前全世界最高发的恶性肿瘤之一，乙型肝炎病毒（HBV）是引起肝癌和术后复发的重要病因，因此研究HBV引发肝癌和术后复发的机制具有重要临床意义。研究发现具有胞苷脱氨酶活性的APOBEC3B (A3B)基因可编辑HBV DNA，并和干扰素相互作用，参与固有免疫发挥抑制HBV的作用。我们的前期实验显示A3B的缺失突变和HBV持续性感染以及HBV相关肝癌的发生危险相关,但A3B对乙肝相关性肝癌的发生发展及具体作用机制尚不清楚。本项目拟在前期实验的基础上，在肝癌组织标本中研究A3B蛋白表达量与HBV相关性肝癌的预后、术后复发及干扰素治疗反应的关系，通过体外实验研究A3B与HBV复制、干扰素、肝癌生物学特性之间的关系。

肝细胞肝癌是目前全世界最高发的恶性肿瘤之一，乙型肝炎病毒（HBV）是引起肝癌和术后复发的重要病因，因此研究HBV引发肝癌和术后复发的机制具有重要临床意义。研究发现具有胞苷脱氨酶活性的APOBEC3B (A3B)基因可编辑HBV DNA，并和干扰素相互作用，参与固有免疫发挥抑制HBV的作用。我们的前期实验显示A3B的缺失突变和HBV持续性感染以及HBV相关肝癌的发生危险相关,但A3B对乙肝相关性肝癌的发生发展及具体作用机制尚不清楚。本研究首先采集了908名肝癌患者的临床病理学资料，建立了肝癌患者的临床资料数据库，并全部完成了随诊。对该908例肝癌患者的临床病理资料进行生存分析，我们重点研究了BCLC B和C期的患者，这些既往指南不建议行手术的患者，结果发现肿瘤单发、肿瘤发生肝外侵犯或穿破浆膜、肿瘤侵犯大血管或瘤栓以及具有临床症状（ECOG PS 1-2）为患者总生存时间的危险因素。根据以上危险因素分组后，高危组和低危组的生存率和复发率具有显著差异，提示在严格把握手术适应症的前提下，对部分BCLC B和C级患者采取手术治疗，能够获得良好的预后。另外，我们已经完成了其中300例肝细胞肝癌患者的病理组织芯片的制备和染色，初步结果显示肝癌组织中A3B表达高于癌旁组织，结果正在分析中，并同时撰写相关论文。