Wu Meng-Yu, Yiang Giuo-Teng, Cheng Pei-Wen, Chu Pei-Yi, Li Chia-Jung
Department of Emergency Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan.
Department of Emergency Medicine, School of Medicine, Tzu Chi University, Hualien 970, Taiwan.
J Clin Med. 2018 Aug 13;7(8):213. doi: 10.3390/jcm7080213.
Hepatocarcinogenesis comprises of multiple, complex steps that occur after liver injury and usually involve several pathways, including telomere dysfunction, cell cycle, WNT/β-catenin signaling, oxidative stress and mitochondria dysfunction, autophagy, apoptosis, and AKT/mTOR signaling. Following liver injury, gene mutations, accumulation of oxidative stress, and local inflammation lead to cell proliferation, differentiation, apoptosis, and necrosis. The persistence of this vicious cycle in turn leads to further gene mutation and dysregulation of pro- and anti-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-10, IL-12, IL-13, IL-18, and transforming growth factor (TGF)-β, resulting in immune escape by means of the NF-κB and inflammasome signaling pathways. In this review, we summarize studies focusing on the roles of hepatocarcinogenesis and the immune system in liver cancer. In addition, we furnish an overview of recent basic and clinical studies to provide a strong foundation to develop novel anti-carcinogenesis targets for further treatment interventions.
肝癌发生由肝损伤后发生的多个复杂步骤组成，通常涉及多个途径，包括端粒功能障碍、细胞周期、WNT/β-连环蛋白信号传导、氧化应激和线粒体功能障碍、自噬、凋亡以及AKT/mTOR信号传导。肝损伤后，基因突变、氧化应激积累和局部炎症导致细胞增殖、分化、凋亡和坏死。这种恶性循环的持续反过来导致进一步的基因突变以及促炎和抗炎细胞因子（如白细胞介素（IL）-1β、IL-6、IL-10、IL-12、IL-13、IL-18和转化生长因子（TGF）-β）的失调，通过NF-κB和炎性小体信号通路导致免疫逃逸。在本综述中，我们总结了关注肝癌发生和免疫系统在肝癌中作用的研究。此外，我们概述了最近的基础和临床研究，为开发新的抗癌发生靶点以进行进一步治疗干预提供坚实基础。
