DEN-induced rat model reproduces key features of human hepatocellular carcinoma

Using RNA-seq analysis, we study a DEN-induced HCC rat model during fibrosis progression and HCC development with special focus on liver inflammatory microenvironment. RNA-seq results show that DEN-induced liver tumors in rat model share remarkable molecular characteristics with human HCC, especially with HCC associated with high proliferation. In conclusion, our study provides detailed insight into the hepatocarcinogenesis in a commonly used model of HCC, facilitating the future use of this model for preclinical testing. Overall design: 7-week-old Fischer 344 male rats were treated weekly with intra-peritoneal injections of 50 mg/kg DEN. We analysed 3 different time points of DEN treatment: i) after 8 weeks of DEN injections (DEN08), ii) after 14 weeks of DEN injections (DEN14) and iii) after 14 weeks of DEN injection followed by 6 weeks of no DEN injection (DEN20). Animals of the same age, treated with no DEN were used as controls for 8 weeks (NOD08), 14 weeks (NOD14) and 20 weeks time points (NOD20). Non-tumoral (NT) tissues and Tumoral (T) tissues were analysed separately.

本研究通过RNA测序（RNA-seq）分析，针对二乙基亚硝胺（DEN）诱导的肝细胞癌（HCC）大鼠模型，探究其在纤维化进展与肝癌发生过程中的肝脏炎症微环境，重点聚焦该微环境特征。RNA测序结果显示，该大鼠模型中DEN诱导的肝脏肿瘤与人类肝细胞癌（HCC）具有显著相似的分子特征，尤其与高增殖型肝细胞癌高度吻合。综上，本研究深入阐明了这一常用肝细胞癌模型的肝癌发生机制，可为该模型后续应用于临床前测试提供有力支撑。
实验设计如下：将7周龄的Fischer 344雄性大鼠每周一次腹腔注射50 mg/kg的DEN。本研究选取DEN处理的三个不同时间节点开展分析：① 接受8周DEN注射后（DEN08组）；② 接受14周DEN注射后（DEN14组）；③ 接受14周DEN注射后停药6周（DEN20组）。同时选取同周龄未接受DEN处理的大鼠作为对照组，分别对应8周（NOD08组）、14周（NOD14组）及20周（NOD20组）三个时间节点。研究分别对非肿瘤组织（NT）与肿瘤组织（T）进行了独立分析。