胸腺癌血浆外泌体miRNAs诊断标记物筛选及机制研究

胸腺癌是一种非常罕见、浸润广泛的肿瘤，临床缺乏辅助诊断的生物标记物，由于临床样本及细胞模型的罕见，既往相关的机理性研究甚少。循环外泌体miRNA介导的液体活检在肿瘤诊断中日益深入，但该研究在胸腺癌中仍为空白，我们前期研究表明胸腺癌血浆外泌体miRNA存在其特征谱，血浆外泌体miR-16-5p表达水平具有诊断胸腺癌的潜能，通过预测发现CTNND1为机体miR-16-5p的靶基因，miR-16-5p在胸腺癌中的下调与CTNND1的上调相关联，从而说明体内存在着一种调控机制。本项目拟通过血浆外泌体miRNA测序结合验证筛选一组辅助胸腺癌诊断的生物标记，从细胞模型、动物水平、临床样本三方面，应用各种分子生物学手段明确外泌体miR-16-5p靶向CTNND1在胸腺癌中作用及相关机制，继之回归临床，明确外泌体miR-16-5p在胸腺肿瘤中作为鉴别诊断标记物的可能性，为胸腺癌诊断提供指导和理论依据。

Thymic carcinoma is a very rare and highly metastatic tumor, and there is no biomarker for clinical diagnosis. Due to the rarity of clinical samples and cell models, few studies shed light on the mechanism of thymic cancer. The study of circulating exosomal miRNAs mediated liquid biopsy in tumor diagnosis is increasing in-depth, but it is still blank in thymic cancer. Our previous study shows that there is a characteristic spectrum of exosomal miRNA in thymic cancer, and the expression level of miR-16-5p in exosome has the potential to diagnose thymic cancer. It is predicted that CTNND1 is the target gene of mir-16-5p, and the down-regulation of mir-16-5p in thymic cancer is related to the up regulation of CTNND1, which indicates that there is a regulatory mechanism in vivo. In this project, we intend to screen a group of biomarkers to assist the diagnosis of thymic cancer through the combination of plasma exosome miRNA sequencing and validation. From three aspects of cell model, animal level and clinical samples, we will use various molecular biological tools to clarify the role and related mechanism of exosomal mir-16-5p targeting CTNND1 in thymic cancer, and then go back to clinical practice to clarify the role of exosome mir-16-5p in thymic cancer as a differential marker. The possibility of diagnostic markers can provide guidance and theoretical basis for the diagnosis of thymic cancer.