Comparing mRNA expression between carrier treated and sorafenib treated Myc/NrasG12V liver tumors. Comparing mRNA expression between carrier treated and sorafenib treated Myc/NrasG12V liver tumors

To profile determinants of sensitivity and resistance towards the multikinase inhibitor sorafenib in liver cancer (HCC), we generated HCCs with elevated MYC expression and activated Raf-MEK-ERK signaling. To trigger tumor development, we co-delivered transposable elements encoding for Myc and oncogenic NrasG12V via hydrodynamic injection into the hepatocytes of C57BL/6 wildtype mice. To characterize the response of Myc/NrasG12V HCCs towards sorafenib, we analyzed their transcriptomes after three weeks of sorafenib or carrier treatment. Overall design: mRNA expression of carrier treated and sorafenib treated Myc/NrasG12V liver tumors was compared via mRNAseq analysis

为解析肝癌（hepatocellular carcinoma, HCC）对多激酶抑制剂索拉非尼（sorafenib）的敏感性与耐药性决定因素，我们构建了MYC高表达且Raf-MEK-ERK信号通路激活的肝癌模型。为诱导肿瘤发生，我们通过水动力注射（hydrodynamic injection）将编码Myc与致癌性NrasG12V的转座元件（transposable elements）共同递送至C57BL/6野生型小鼠的肝细胞中。为表征Myc/NrasG12V型肝癌对索拉非尼的应答反应，我们对接受索拉非尼或载体处理三周后的肝癌组织转录组进行了分析。整体实验设计：通过mRNA测序（mRNAseq）比较载体处理组与索拉非尼处理组Myc/NrasG12V肝肿瘤的mRNA表达谱。