MRI影像组学评估结直肠癌上皮间质转化及microRNA-34a靶向治疗疗效的研究

Colorectal cancer (CRC) is one of the common malignant tumors in the gastrointestinal tract, with the third highest incidence in the world. Distant metastasis and chemoresistance are the main factors affecting the prognosis. The 5-year survival rate of metastatic CRC patients is less than 10%. Epithelial-mesenchymal transition (EMT) plays an important role in the distant metastasis and chemoresistance in patients with CRC. microRNA-34a can be used as an important inhibitor regulating EMT. Targeted therapy of EMT with microRNA-34a can inhibit the invasion and metastasis of tumors, which is expected to be the target of tumor therapy. MRI-based radiomics can be used to extract invisible image features within the lesion and perform quantitative analysis to evaluate the micro-environment changes noninvasively, revealing the intrinsic characteristics of tumors, the changes caused by intervention and the impact on prognosis of patients. In this study, MRI radiomics will be utilized to evaluate CRC EMT in patients and targeted therapy efficacy with microRNA-34a in xenografts models. The optimal model will be established to provide the noninvasive method for the future evaluation of EMT and anti-EMT in patients with CRC, which is important for the clinical transformation.

结直肠癌(colorectal cancer，CRC) 全球发病率位居第三位。远处转移、化疗耐药是影响患者预后的主要因素，转移性CRC患者的5年生存率低于10%。上皮间质转化(epithelial-mesenchymal transition，EMT)是CRC远处转移和化疗耐药的重要机制。microRNA-34a可作为调控EMT的重要抑制剂，从而抑制肿瘤的侵袭和转移，有望成为今后抗EMT治疗新策略。基于MRI的影像组学可提取病灶内部不可视影像特征，并进行定量分析，揭示肿瘤内在本质特性、干预引起的变化及对患者预后的影响。因此，本项目拟采用MRI影像组学对CRC患者肿瘤中EMT进行临床评估，建立影像组学评估模型；并采用MRI影像组学评估对CRC进行microRNA-34a靶向EMT的治疗疗效，为今后临床CRC患者接受抗EMT治疗及其评估提供无创性方法，具有重要的临床转化价值。

结直肠癌(colorectal cancer，CRC)是消化道常见的恶性肿瘤之一，全球发病率位居第三位。远处转移、化疗耐药是目前影响患者预后的主要因素，上皮间质转化(epithelial-mesenchymal transition，EMT)是CRC远处转移和化疗耐药的重要机制。microRNA-34a可作为调控EMT的重要抑制剂，从而抑制肿瘤的侵袭和转移，有望成为今后抗EMT治疗新策略。本项目首先采用基于MRI的影像组学，利用其能提取病灶内部不可视影像特征的优势，探索了MRI影像组学评估直肠癌患者肿瘤内EMT的价值，结果显示MRI影像组学模型在训练组和测试组对于肿瘤内EMT的具有一定的诊断价值。在训练组及测试组，受试者工作特征曲线（ROC）曲线下面积（AUC值）分别为0.79、0.72，有助于评估直肠癌肿瘤内的EMT。其次，采用HCT116、SW480细胞株，通过过表达Snail1诱导EMT，并在细胞形态、Western Blot、qPCR方面进行验证，也通过细胞迁移侵袭实验验证了EMT后细胞迁移侵袭能力增高。随后，评估了microRNA-34a靶向EMT的调控作用，结果显示，microRNA-34a的抑制可使E-cadherin蛋白表达降低、Vimentin蛋白表达增高、细胞迁移侵袭能力增高，表明microRNA-34a可靶向EMT的进行调控。第三，探索了MRI影像组学在体评估肿瘤内抗EMT治疗疗效的价值。成功构建了HCT116/Control、HCT116/Snail1和HCT116/ microRNA-34a-mimics组裸鼠皮下移植瘤模型，在MRI清晰显像的前提下，构建了基于MRI的影像组学模型评估肿瘤内EMT变化。结果显示MRI影像组学模型有助于HCT116/Control与HCT116/Snail1、HCT116/Snail1与HCT116/microRNA-34a-mimics组间的鉴别诊断，AUC值分别为0.75、0.72。MRI影像组学有望为结直肠癌抗EMT治疗疗效评估提供新技术参考。. 在本项目执行期间，资助发表SCI论文4篇；1篇论文摘要被第107届北美放射学年会接收为大会口头发言，并线上参会。.