背景:牙源性角化囊肿(OKC)是一种相对常见的牙源性病变,其特征在于上颌骨和下颌骨的局部侵袭。在OKC的病理组织切片中,经常观察到免疫细胞浸润。然而,OKC的免疫细胞谱和免疫细胞浸润的分子机制尚不清楚。我们旨在探索OKC的免疫细胞谱,并探讨OKC中免疫细胞浸润的潜在发病机制。
方法:从基因表达综合(GEO)数据库获得包括OKC和口腔粘膜(OM)样品的微阵列数据集GSE38494。用R软件对OKC中的差异表达基因(DEGs)进行分析。OKC的hub基因通过蛋白质-蛋白质相互作用(PPI)网络进行。通过单样品基因集富集分析(ssGSEA)进行差异免疫细胞浸润以及免疫细胞浸润与hub基因之间的潜在关系。通过免疫荧光和免疫组织化学证实了17个OKC和8个OM样本中COL1A1和COL1A3的表达。
结果:我们共检测到402个差异表达基因(DEG),其中247个上调,155个下调。DEGs主要参与含胶原的细胞外基质通路,外部封装结构组织,和细胞外结构组织。我们确定了十个hub基因,即FN1,COL1A1,COL3A1,COL1A2,BGN,POSTN,SPARC,FBN1、COL5A1和COL5A2。在OM和OKC组之间,八种类型的浸润性免疫细胞的丰度存在显着差异。COL1A1和COL3A1均与自然杀伤T细胞和记忆B细胞呈显著正相关。同时,它们与CD56dim自然杀伤细胞呈显著负相关,中性粒细胞,未成熟树突状细胞,和激活的树突状细胞。免疫组织化学分析显示,与OM相比,OKC中的COL1A1(P=0.0131)和COL1A3(P<0.001)明显升高。
结论:我们的发现为OKC的发病机制提供了见解,并阐明了这些病变内的免疫微环境。关键基因,包括COL1A1和COL1A3,可能会显著影响与OKC相关的生物过程。
Odontogenic keratocyst (OKC) is a relatively common odontogenic lesion characterized by local invasion in the maxillary and mandibular bones. In the pathological tissue slices of OKC, immune cell infiltrations are frequently observed. However, the immune cell profile and the molecular mechanism for immune cell infiltration of OKC are still unclear. We aimed to explore the immune cell profile of OKC and to explore the potential pathogenesis for immune cell infiltration in OKC.
The microarray dataset GSE38494 including OKC and oral mucosa (OM) samples were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) in OKC were analyzed by R software. The hub genes of OKC were performed by protein-protein interaction (PPI) network. The differential immune cell infiltration and the potential relationship between immune cell infiltration and the hub genes were performed by single-sample gene set enrichment analysis (ssGSEA). The expression of COL1A1 and COL1A3 were confirmed by immunofluorescence and immunohistochemistry in 17 OKC and 8 OM samples.
We detected a total of 402 differentially expressed genes (DEGs), of which 247 were upregulated and 155 were downregulated. DEGs were mainly involved in collagen-containing extracellular matrix pathways, external encapsulating structure organization, and extracellular structure organization. We identified ten hub genes, namely FN1, COL1A1, COL3A1, COL1A2, BGN, POSTN, SPARC, FBN1, COL5A1, and COL5A2. A significant difference was observed in the abundances of eight types of infiltrating immune cells between the OM and OKC groups. Both COL1A1 and COL3A1 exhibited a significant positive correlation with natural killer T cells and memory B cells. Simultaneously, they demonstrated a significant negative correlation with CD56dim natural killer cells, neutrophils, immature dendritic cells, and activated dendritic cells. Immunohistochemistry analysis showed that COL1A1 (P = 0.0131) and COL1A3 (P < 0.001) were significantly elevated in OKC compared with OM.
Our findings provide insights into the pathogenesis of OKC and illuminate the immune microenvironment within these lesions. The key genes, including COL1A1 and COL1A3, may significantly impact the biological processes associated with OKC.