成釉细胞瘤（AB）是颌面部最常见的侵袭性牙源性肿瘤，具有高复发率。依据课题组对本科室病例回顾分析，AB复发率高达37%。明确AB侵袭分子及细胞学机制，将为发现AB干预或治疗新策略提供理论依据。申请者前期通过AB病人样本转录组学测序筛选及后续组织学验证，发现了缺氧诱导因子1α（HIF-1α）在AB中表达明显上调且与复发呈现正相关；通过基因相互作用关系网络和共表达基因富集分析，发现HIF-1α、上皮-间质转化（EMT）、“干细胞自我更新特性”三者涉及的关键分子具有明显关联性。基于此，我们提出假说：HIF-1α及其相关分子异常表达促进AB侵袭，而该肿瘤中存在的高侵袭异质性干细胞样细胞亚群则是AB侵袭、复发的细胞学基础。本项目将通过新一代高通量测序和大样本分析，并利用动物模型、细胞学和分子生物学手段验证该假说，来阐明AB侵袭分子机制和相关细胞亚群，为AB的临床诊疗发掘潜在的预后标志物和可干预靶点。

Ameloblastoma (AB) is the most common invasive odontogenic tumor within oral maxillofacial region.The recurrence rate is relatively high. Our retrospective data revealed the recurrence rate for AB is as high as 37%. Thereby, understanding the molecular and cellular mechanisms of invasive AB might be able to guide us new strategies on early intervention and treatment planning. Our preliminary study on AB genome sequencing screening and tissue samples had found out that overexpression of hypoxia inducible factor 1 alpha (HIF-1α) was correlated to tendency of tumor recurrence. On the other hand, gene interaction network and co-expression analysis showed key molecules involved in HIF-1α, epithelial mesenchymal transition (EMT) and "stem cell self-renewal properties" were significantly correlated. Therefore, we proposed a hypothesis that HIF-1α and related molecules in the abnormal expression and contribute to the invasiveness of AB; at the same time, the tumors appeared high invasive and heterogeneity of cell subsets, and the subsets is the cytological basis of AB invasion, recurrence, as potential therapeutic targets. We therefore propose a study based on a new generation of high-throughput sequencing, animal models, cytology and molecular biology methods to verify underlining molecular mechanism and the correlated cell subsets. This is to assist in clinical diagnosis, identifying the potential prognostic markers and therapeutic targets.