IncRNA促甲状腺乳头状癌淋巴结转移的机制及US-FNAB-lncRNA联合诊断的价值研究

Modern ultrasound （US）technology and ultrasound-guided fine needle aspiration biopsy (US-FNA) are effective methods to diagnose papillary thyroid carcinoma (PTC) in the early stage. However, the presence or absence of early cervical lymph nodes metastasis（LNM）of PTC,which cannot be detected by ultrasound is a major determinant of treatment option and disease prognosis. A lot of studies have demonstrated that lncRNAs play a critical role in cancer metastasis. Based on the transcriptome-wide lncRNAs expression profile analysis of human PTCs with or without LNM, our preliminary study found a new lncRNA NONHSAT076754, which is upregulated in metastasized PTC and promotes migration and invasion in vivo. In addition, our study identified that NONHSAT076754 modulates migration and invasion through fibronectin-1 which is a downstream regulator. The aim of this project is to investigate the mechanism of NONHSAT076754 in PTC metastasis and the diagnostic value of US-FNAB-NONHSAT076754.We would try to find how they regulate lymph nodes metastasis in PTC by using cell lines and US mediated animal model. We would also study the combined diagnostic value of NONHSAT076754 with US-FNAB, prospecting that the proposed study will help generate better clinical protocol for preoperative evaluation, and treatment option.

现代超声技术是诊断甲状腺乳头状癌（PTC）的有效手段，但是否存在超声不可探测的颈部淋巴结转移是未解决的问题之一。超声引导细针穿刺抽吸（US-FNAB）结合分子标记物分析可改善这一状况。本课题组基于对转移性和非转移性甲状腺乳头状癌组织RNA表达谱分析鉴定，筛选出在转移PTC中显著高表达的lncRNA NONHSAT076754， 初步功能实验提示其具有促进PTC侵袭转移的作用，并与侵袭相关基因FN1的表达相平行。本申请拟进一步1）建立稳定的超声介导转移PTC动物模型；2）利用甲癌细胞株和动物模型探索NONHSAT076754在PTC转移过程的机制；3）进行大样本临床调查评估US-FNAB联合NONHSAT076754分子标记物预测转移倾向的价值。 我们期望这项研究将有助于优化诊断甲状腺乳头状癌术前评估流程，并为开展转移性甲状腺乳头状癌靶向治疗提供潜在靶点。

现代超声技术是诊断甲状腺乳头状癌（PTC）的有效手段，但是否存在超声不可探测的颈部淋巴结转移是未解决的问题之一。超声引导细针穿刺抽吸（US-FNAB）结合分子标记物分析可改善这一状况。本课题组基于对转移性和非转移性甲状腺乳头状癌组织RNA表达谱分析鉴定 ，筛选出在转移PTC中显著高表达的lncRNA NONHSAT076754，初步功能实验提示其具有促进PTC侵袭转移的作用，进一步体外功能实验表明其下游基因FN1、TWSG1的敲低和过表达也分别抑制和促进癌细胞的增殖、侵袭、迁移等能力，TWSG1还促进肿瘤血管因子和基质降解酶的表达，NONHSAT076754通过ceRNA机制发挥促癌作用。对甲状腺乳头状癌超声图像分析发现超声图像评估甲状腺乳头状癌淋巴结转移的准确性为65.72%；NONHSAT076754、FN1、TWSG1的高表达与甲状腺乳头状癌淋巴结转移有关；FN1、TWSG1术前预测淋巴结转移的准确性分别为81.1%、78.0%，US-FNA-NONHSAT076754术前诊断甲状腺乳头状癌淋巴结转移的准确性为87.5%。我们期望这项研究将有助于优化诊断甲状腺乳头状癌术前评估流程，并为开展转移性甲状腺乳头状癌靶向治疗提供潜在靶点。