颈淋巴转移是影响口腔癌预后的主要因素，课题组临床试验发现近30%的早期口腔癌出现隐匿性颈转，亟需能从机制上解释的生物标志物提供早期预警进而有效治疗。全转录组芯片筛选发现微丝相关蛋白5（MFAP5）在转移患者的原发癌组织中高表达，并在mRNA和蛋白水平证实与转移和生存预后相关；缺氧培养可使口腔癌细胞系中MFAP5表达上调，是探究其表达升高及促进转移分子机制的可能切入点。查阅文献Notch通路可由缺氧相关因子HIF-1α激活，也可介导MFAP5发挥胞内功能。因此我们提出口腔癌中MFAP5可能与HIF-1α/Notch通路形成正反馈环路，上调表达并促进转移。本研究拟通过功能性拯救实验与裸鼠模型，研究MFAP5对口腔癌细胞侵袭转移能力的影响，以缺氧诱导的HIF-1α/Notch通路为切入点，探讨MFAP5上调及促进转移的分子机制，与临床样本验证相结合，提供其作为口腔癌转移早期预警标记物的实验依据。

Metastasis is mainly accounts for treatment prognosis of oral cancer. Occult cervical lymphatic metastasis is nearly 30% in oral squamous cell carcinoma with early stage (cT1-2N0M0). The key point is to seek out biomarker to distinguish the groups who can benefits from the treatment. The biomarker should explain the mechanism of metastasis before clinical application. Our research group has completed comparative transcriptomics for tumor and normal tissues from patients with or without occult cervical lymphatic metastasis. The results showed that microfibrillar-associated protein 5(MFAP5) is obvious highly expressed in tumor tissue of occult cervical lymphatic metastasis group and also in cell line which has been considered with highly metastatic potential. All this results have been validated in mRNA and protein levels, and MFAP5 is correlation with prognosis and metastasis. Hypoxia micro-environment can elevate the expression of MFAP5 in oral cancer cells, which was potential for further mechanism research of its up-regulation and metastasis. It has been reported that Notch signaling can be activated by up-regulated HIF-1α during hypoxia-environment and also mediate intracellular function of MFAP5 binding with its ligand or receptor. Thus we hypothesize that a positive feedback loop may be present between MFAP5 and HIF-1α/Notch pathway in hypoxia environment, which promoting metastasis. Based on our previous results, we main to focus on the HIF-1α/Notch signal pathway which was induced in hypoxia environment and to explore the molecular mechanism of up-regulation and metastasis promoting ability of MFAP5 in oral squamous cell carcinoma by in-vivo and in-vitro studies and further to validate it in patients. Our research will provide an experimental evidence for the selection of early stage metastasis biomarkers in oral squamous cell carcinoma.