肝细胞癌是我国常见的恶性高发肿瘤之一，代谢功能和线粒体稳态改变是肝细胞癌发生发展及恶性转变的重要影响因素。线粒体自噬是维持线粒体稳态的重要途径，研究其在肝细胞癌中的变化及其调控机制具有重要意义。肝细胞癌中Gankyrin-Nrf2通路能够清除ROS、拮抗细胞凋亡并促进肝癌发展。前期我们发现在细胞水平Gankyrin-Nrf2能够增加肝细胞癌线粒体的数量、增强线粒体呼吸功能并抑制线粒体自噬过程。本项目拟在前期工作基础上在临床样本水平明确Gankyrin-Nrf2抑制线粒体自噬过程的临床病理学意义；采用分子生物学方法明确其分子机制；最终结合实验动物模型研究Gankyrin-Nrf2抑制线粒体自噬进而促进肝细胞癌发展的作用。本课题的实施有助于明确Gankyrin-Nrf2通路抑制线粒体自噬过程在线粒体稳态、肝癌发生发展中的作用及其作为肝细胞癌潜在治疗靶标的治疗价值，为后续转化医学研究奠定基础。

Hepatocellular carcinoma (HCC) is a common type of malignant tumor in China. Disorders of metabolism and mitochondrial is significant to the tumorigenesis and malignant of HCC. Mitophagy is important to the homeostasis of mitochondrial. It’s consequential to find the alternation and mechanism of mitophagy in HCC. We have found that Gankyrin-Nrf2 could increase the quantity and function of mitochondria and inhibit mitophaghy. One hand, this research intends to validate the effect of Gankyrin-Nrf2 on mitochondria and mitophagy in clinical samples. On the other hand, we want to find the molecular mechanism which Gankyrin-Nrf2 inhibits mitophagy and its meaning in the tumorigenesis and progression of HCC. This work could identify the effect of Gankyrin-Nrf2-mitophagy in the tumorigenesis of HCC and the underlying value of Gankyrin-Nrf2 in the therapy of HCC.