基于MR影像组学预测肝细胞癌上皮间质转化及microRNA-125b靶向治疗疗效的实验研究

肝细胞癌（HCC）复发转移率高，易对常规化学药物产生耐药性，是当前临床治疗的瓶颈。上皮间质转化（EMT）是HCC发生侵袭转移，形成耐药性的关键因素。但目前尚无预测肝细胞癌EMT的非侵入性检测方法。我们前期研究证实影像组学方法可以鉴别HCC的E-S病理分级及微血管浸润，是一种有潜力的数字化活检技术；同时，文献及我们预实验表明microRNA-125b可以抑制HCC发生EMT。基于此，我们提出假说：MR影像组学可以预测肝细胞癌EMT和microRNA-125b靶向治疗疗效。本课题首先基于裸鼠人肝癌皮下成瘤实验，利用影像组学方法，构建肝细胞癌EMT预测模型。进一步，采用荷瘤裸鼠microRNA-125b治疗实验，探讨肝细胞癌EMT预测模型动态评估microRNA-125b治疗疗效的可行性。本课题为无创性评估肝细胞癌EMT和实时监测抗EMT靶向治疗疗效提供新的思路和方法，为临床转化提供理论依据。

Hepatocellular carcinoma (HCC) has been challenging to treat because it tends to recur  and metastasize frequently and develop chemoresistance. Epithelial-mesenchymal transformation (EMT) contributes to tumor invasion and metastasis, as well as chemoresistance, including in HCC. Unfortunately, there is no non-invasive method capable of accurately identifying HCC with EMT. Our previous studies have confirmed that radiomics has the potential to identify Edmondson-Steiner pathological grade and microvascular invasion of HCC. Literature reports and our previous studies have demonstrated that microRNA-125b exerts inhibitory effects on EMT in HCC. Based on these results, we hypothesized that MR imaging-based radiomics model could detect HCC with EMT and evaluate efficacy of microRNA-125b on HCC as potential noninvasive biomarkers. In this study, a radiomics model for the identification of HCC with EMT will be established and validated initially, based on MR images of subcutaneous transplantation HCC models. MicroRNA-125b therapeutic studies in vivo will be further conducted to explore the correlation between the radiomics model and EMT markers at different stages. This project will provide novel ideas and strategies for non-invasive detection of HCC with EMT and real-time monitoring of the efficacy of anti-EMT targeted therapy, as well as theoretical basis for clinical transformation.