临床证据显示肿瘤相关抗原自身抗体在肿瘤早期诊断中具有重要价值，但缺乏相关机制研究。本课题组前期研究发现CENPF自身抗体检测早期HCC具有较高敏感度和特异性，并发现HCC细胞内CENPF蛋白过表达和异常定位，CENPF在细胞内的转位与凋亡过程有关，但这些是否与其自身抗体产生相关尚不清楚，凋亡如何介导CENPF胞内转位、暴露并诱导抗体产生有待研究。我们假设过表达的CENPF通过细胞凋亡转位并诱导自身抗体产生。本课题首先在体内外研究CENPF蛋白表达水平与异常定位的关联，以及与免疫系统激活、自身抗体产生的相关性；其次明确凋亡过程中过表达的CENPF在胞内转位和质膜暴露方式；最后分离不同凋亡组分，检测其促进免疫细胞摄取活化、诱导免疫系统激活和CENPF抗体产生的能力。本研究有助于揭示CENPF抗原暴露和自身抗体产生的机制，为CENPF等肿瘤相关抗原自身抗体在临床诊断中的应用提供理论和实验依据。

Tumor associated antigen autoantibodies have advantages in early diagnosis of tumor, but the mechanism is unclear. Our research group have screened out CENPF autoantibody with high sensitivity and specificity in early hepatocellular carcinoma (HCC) diagnosis, and found that CENPF protein showed abnormal expression and localization features in the tumor tissue, and that CENPF translocation was related to apoptosis. It is unclear whether these features are associated with autoantibodies production, and how intracellular protein CENPF exposures to the immune system and induces autoantibody production through apoptosis. We hypothesis highly expressed CENPF translocates outside the cells through apoptosis and induces autoantibody production. First, using HCC cells and tumor mouse model, we analyze the relationship between CENPF abnormal expression and cellular location, and its correlation with immune system activation and autoantibody production; secondly, we explore how CENPF protein translocates outside the cells and exposures on cell membrane through apoptosis; finally, we separate different apoptotic components and detect their effect on activation of immune cells and system, and the production of CENPF antibody. The study findings will help to reveal the mechanism of CENPF antigen exposure and autoantibody generation, and provide theoretical and experimental basis for application of CENPF autoantibody in the clinical diagnosis.