Erratum: Validation of a Preclinical Model of Diethylnitrosamine-Induced Hepatic Neoplasia in Yucatan Miniature Pigs

<b><i>Objective:</i></b> The purpose of this study was to reduce the time to tumor onset in a diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) swine model via partial liver embolization (PLE) and to characterize the model for use in translational research. <b><i>Methods:</i></b> Eight Yucatan miniature pigs were injected intraperitoneally with either saline (n = 2) or DEN (n = 6) solution weekly for 12 weeks. Three of the DEN-treated pigs underwent PLE. The animals underwent periodic radiological evaluation, liver biopsy, and blood sampling, and full necropsy was performed at study termination (∼29 months). <b><i>Results:</i></b> All DEN-treated pigs developed hepatic adenoma and HCC. PLE accelerated the time to adenoma development but not to HCC development. Biomarker analysis results showed that IGF1 levels decreased in all DEN-treated pigs as functional liver capacity decreased with progression of HCC. VEGF and IL-6 levels were positively correlated with disease progression. Immunohistochemical probing of HCC tissues demonstrated the expression of several important survival-promoting proteins. <b><i>Conclusion:</i></b> To our knowledge, we are the first to demonstrate an accelerated development of hepatic neoplasia in Yucatan miniature pigs. Our HCC swine model closely mimics the human condition (i.e., progressive disease stages and expression of relevant molecular markers) and is a viable translational model.

**研究目的：** 本研究旨在通过部分肝栓塞术（partial liver embolization, PLE）缩短二乙基亚硝胺（diethylnitrosamine, DEN）诱导的肝细胞癌（hepatocellular carcinoma, HCC）猪模型的肿瘤发生时间，并对该模型进行表征以用于转化研究。
**研究方法：** 8只尤卡坦小型猪每周接受腹腔注射，分别给予生理盐水（n = 2）或二乙基亚硝胺溶液（n = 6），持续12周。其中3只经二乙基亚硝胺处理的猪实施了部分肝栓塞术。实验动物定期接受影像学评估、肝活检及血液采样，并在实验结束时（约29个月）进行全面尸检。
**研究结果：** 所有经二乙基亚硝胺处理的猪均出现肝腺瘤及肝细胞癌。部分肝栓塞术可加速肝腺瘤的发生进程，但未缩短肝细胞癌的发生时长。生物标志物分析结果显示，随着肝细胞癌进展导致肝功能下降，所有处理组猪的胰岛素样生长因子1（IGF1）水平均降低；血管内皮生长因子（VEGF）与白细胞介素6（IL-6）水平与疾病进展呈正相关。对肝细胞癌组织的免疫组化检测证实，多种重要的促存活蛋白均有表达。
**研究结论：** 据我们所知，本研究首次证实尤卡坦小型猪的肝脏肿瘤发生进程可被加速。本研究构建的肝细胞癌猪模型可高度模拟人类疾病状态（即进行性疾病分期及相关分子标志物表达），是一种可行的转化研究模型。