甲状腺癌在我国的发病率呈逐年上升趋势，其中甲状腺乳头状癌（PTC）最为常见。如何早期评估PTC侵袭性以选择合适治疗方案具有重要临床意义。约50%-70% PTC存在BRAF V600E 基因突变，但仅凭该突变状态不足以评估PTC侵袭性。本项目拟探索能够与BRAF V600E 基因突变协同影响PTC 侵袭性的分子生物学因素。我们通过分析PTC基因表达谱数据，发现细胞外基质蛋白POSTN及基质金属蛋白酶MMP13在BRAF V600E突变型PTC高表达，且与肿瘤侵袭性相关。既往研究显示POSTN可激活AKT信号通路，但POSTN是否通过激活AKT信号通路，并且与BRAF V600E突变相协同而上调MMP13，进而增加PTC侵袭性尚不明确。本项目拟结合体外及体内实验，探讨POSTN/AKT通路在BRAF V600E突变型PTC侵袭性中的作用及机制，为PTC早期侵袭性诊断提供理论基础。

The incidence of Papillary thyroid cancer (PTC) is rapidly growing in China. Identifying aggressive PTCs with the potential of post-surgical recurrence is the main challenge of medical practice. Though BRAF V600E mutation is found in 50-70% of PTCs, this mutation status is not sufficient to predict tumor aggressiveness. By analyzing the expression profile of PTC patients, we found that ECM protein POSTN is associated with the tumor aggressiveness in PTCs with BRAF V600E. Combining previous reports and our findings, we hypothesize that in BRAF V600E-mutated PTCs, POSTN may enhance tumor aggressiveness by activating the AKT pathway and increasing MMP13 expression. Our study aims to find molecular alterations that cooperate with BRAF V600E in mediating tumor aggressiveness, in order to provide new aspects for early PTC risk stratification.