颌骨牙源性角化囊性瘤的定量蛋白质组学研究

Keratocystic odontogenic tumors (KCOTs) are relatively common lesions in the jaws with an intrinsic higher growth potential and proclivity for recurrence. The majority of KCOTs arise sporadically in solitary form while the multiple form usually acts as a feature of the inherited nevoid basal cell carcinoma syndrome (NBCCS).Our previous studies showed that nearly 26% of sporadic KCOTs and 80% of NBCCS-associated KCOTs harbored PTCH1 mutation and/or loss of heterozygosity (LOH). Recently, mutations or LOH of PTCH1 were also reported in other odontogenic cysts,such as dentigerous cyst.Therefore,the current evidence indicates that PTCH1 gene inactivation is not a KCOT exclusive alteration and there are other important genes and mechanisms involved in KCOT progress.To identify potential key proteins and signaling pathways that play critical roles in KCOTs, we will perform protein expression profiling of KCOTs by LC-MS/MS, compared with other odontogenic cysts.We will classify these differential expression proteins into functional related gene groups. Then we will evaluate the potential role of proteins with altered expression in the KCOT formation and progression.The studies will facilitate understanding the mechanisms underlying the development of KCOTs.

牙源性角化囊性瘤（KCOT）是一种常见的颌骨牙源性病损，临床上易复发，可导致颌骨的严重破坏，一般单发，也可伴发痣样基底细胞癌综合征(NBCCS)。本课题组前期研究发现，约26%的散发型KCOT与80%的NBCCS相关KCOT上皮中存在PTCH1基因突变或/和杂合性缺失，而另外70%以上的散发型KCOT至今病因未明。这提示我们，除了PTCH1失活以外，KCOT存在其他未知的致病基因及机制。本研究拟采用串联质谱LC-MS/MS技术，以其他牙源性发育性囊肿为对照，从蛋白质水平高通量筛选KCOT中的差异表达蛋白，对差异表达蛋白进行功能和信号通路聚类分析，利用Realtime PCR和Western blot方法在更多病例中验证表达，进而研究相关蛋白在KCOT发生发展中可能发挥的作用，探索KCOT潜在的新的分子致病机制。

牙源性角化囊性瘤(keratocystic odontogenic tumor, KCOT)是颌骨常见的牙源性肿瘤，可单发或多发，后者常伴发痣样基底细胞癌综合征(nevoid basal cell carcinoma syndrome, NBCCS)，术后易复发。纤维囊壁在肿瘤发生发展过程中均发挥重要的作用。通过对综合征型及非综合征型KCOT囊壁成纤维细胞蛋白质谱检测，筛选得到与骨代谢密切相关的差异蛋白SPARC在综合征型KCOT囊壁成纤维细胞中表达下调，可能与其负向骨代谢特征密切相关。NBCCS患者骨密度值检测结果，发现NBCCS患者骨密度值低于正常对照人群，携带PTCH1蛋白截断型突变的患者骨密度降低更显著，差异具有统计学意义。研究提示,SPARC 表达下调与 PTCH1 突变导致剂量不足密切相关，进一步影响 NBCCS 患者骨密度水平.