YAP1对高发区鼻咽癌合并HBV感染易转移的调节作用及机制研究

Southern China, especially Guangdong Province, is not only the area of high incidence of EBV associated nasopharyngeal carcinoma (NPC), but also an epidemic area of hepatitis caused by HBV, our recent clinical study represent that HBV infection is widespread in NPC population, more likely to occur in young male patients. We found that these patients have some unique clinical characteristics with high risk of metastasis and poor prognosis, and the metastatic form and the immune function are different compared with EBV infection. However, the relevant mechanisms have not yet been elucidated. Using the protein chip platform and bioinformatics tools, we found that YAP1 may be a key molecule to promote metastasis for NPC with HBV infection. Based on our previous study, this project is conductted to explore the role of YAP1, as a oncogene protein, promoting distant metastases in NPC with HBV infection. We hope this study can reveal the mechanism of metastasis for NPC with HBV infection, providing a novel theoretical basis for its clinical diagnosis and treatment.

华南地区不仅是EBV相关鼻咽癌的高发区域，同时也是HBV导致的乙型病毒性肝炎的流行病区，我们的前期临床回顾性研究显示HBV感染在鼻咽癌人群也普遍存在，鼻咽癌合并HBV感染更易好发于年轻男性，这部分患者具有治疗后转移风险高、预后差的临床特点，且在转移形式和免疫功能方面与EBV感染存在差异。然而，目前其相关机制还尚未被阐明，利用蛋白芯片平台及生物信息学工具，我们发现YAP1可能是导致鼻咽癌合并HBV易转移的关键分子。本研究拟在前期研究基础上，进一步通过体内外实验详细阐述YAP1作为一种促癌蛋白，导致鼻咽癌合并HBV感染发生远处转移，对揭示高发区鼻咽癌合并HBV易转移的机制有重要意义，为以后的临床诊治提供新的理论依据。

高发区合并HBsAg阳性鼻咽癌的远处转移率高，生存率低，但其分子机制尚未阐明。在本研究中，我们分析了转移性和非转移性鼻咽癌标本中的差异蛋白表达水平，发现（yes相关蛋白1）YAP1在HBsAg阳性标本中的表达高于HBsAg阴性标本，采用临床标本验证了YAP1可作为鼻咽癌远期生存的预后因子，体内实验验证干扰YAP1可以抑制肿瘤细胞的克隆增殖以及浸润，并且可以调节上皮-间质转化（EMT），且发现HBV X蛋白（HBx）可通过上调YAP1，进一步促进细胞的侵袭性，用荧光素酶报告法证实YAP1是HBx的直接靶点。体内实验也发现干扰YAP1也能减少小鼠体内转移。综上，提示YAP1可能是参与鼻咽癌合并乙肝出现临床易转移的一个重要的分子机制，YAP1可能成为鼻咽癌治疗的一个潜在靶点。