Molecular mechanism of tumorigenesis of cholangiocarcinoma induced by Opisthorchis viverrini infection

本研究通过建立后睾吸虫病相关性胆管癌（CCA）动物模型，并对泰国发病地区患者的CCA肿瘤组织进行分析，寻找与肿瘤发生相关的基因和信号通路，以及与肿瘤分期、转移和生存相关的生物标志物。该研究揭示了猫尾后睾吸虫感染引起的慢性炎症降低解毒能力，导致ROS和蠕虫毒素产物积累，导致DNA损伤、表观遗传和甲基化，以及促进细胞增殖、分化、转化和癌变的基因表达改变的分子机制。

In the present study, by using animal model of opisthorchiasis-associated cholangiocarcinoma(CCA) and the analysis of CCA tumor tissues of the patients from epidemic areas in Thailand, the genes and signaling pathways to involve in the tumorigenesis, and the biomarkers correlated with stage, metastasis and survival were identified. The study revealed the molecular mechanism that chronic inflammation caused by Opisthorchis viverrini infection decreases the ability of detoxination, leading to the accumulation of ROS and the toxin products from worm, which causes DNA damage, epigenesis and methylation, and expression change of the genes that promotes cell proliferation, differentiation, transformation and carcinogenesis.