Fu J, Su Y, Liu Y, Zhang X Y
Department of Oral Medicine, Capital Medical University School of Stomatology, Beijing 100050, China; Institute of Dental Research, Capital Medical University School of Stomatology, Beijing 100050, China.
Institute of Dental Research, Capital Medical University School of Stomatology, Beijing 100050, China.
Zhonghua Kou Qiang Yi Xue Za Zhi. 2018 Apr 9;53(4):248-253. doi: 10.3760/cma.j.issn.1002-0098.2018.04.007.
To compare the methylation profiles in tissues of oral leukoplakia (OLK) and oral squamous cell carcinoma (OSCC) with healthy tissues of oral mucosa, in order to identify the role of DNA methylation played in tumorigenesis. DNA samples extracted from tissues of 4 healthy oral mucosa, 4 OSCC and 4 OLK collected from patients of the Department of Oral Medicine, Capital Medical University School of Stomatology were examined and compared using Methylation 450 Bead Chip. The genes associated with differentially methylated CpG sites were selected for gene ontology (GO) analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment. Multiple differentially methylated CpG sites were identified by using the above mentioned assay. Hypermethylation constitutes 86.18% (23 290/27 025) of methylation changes in OLK and hypomethylation accounts for 13.82% (3 734/27 025) of methylation changes. Both hypermethylated and hypomethylated CpG sites were markedly increased in OSCC tissue compared with OLK tissue. The majority of differentially methylated CpG sites were located outside CpG islands, with approximately one-fourth in CpG shores flanking the islands, which were considered highly important for gene regulation and tumorigenesis. Pathway analysis revealed that differentially methylated CpG sites in both OLK and OSCC patients shared the same pathway enrichments, most of which were correlated with carcinogenesis and cancer progression (e.g., DNA repair, cell cycle, and apoptosis). In the present study, methylation-associated alterations affect almost all pathways in the cellular network in both OLK and OSCC. OLK and OSCC shared similar methylation changes whether in pathways or genes, indicating that epigenetically they might have the same molecular basis for disease progression.
为比较口腔白斑（OLK）和口腔鳞状细胞癌（OSCC）组织与正常口腔黏膜组织中的甲基化谱，以确定DNA甲基化在肿瘤发生中的作用。使用甲基化450K芯片对从首都医科大学口腔医学院口腔内科患者收集的4例正常口腔黏膜、4例OSCC和4例OLK组织中提取的DNA样本进行检测和比较。选择与差异甲基化CpG位点相关的基因进行基因本体（GO）分析和京都基因与基因组百科全书（KEGG）通路富集分析。通过上述检测鉴定出多个差异甲基化的CpG位点。OLK中甲基化变化的86.18%（23290/27025）为高甲基化，13.82%（3734/27025）为低甲基化。与OLK组织相比，OSCC组织中高甲基化和低甲基化的CpG位点均显著增加。大多数差异甲基化的CpG位点位于CpG岛之外，约四分之一位于CpG岛侧翼的CpG岸边，这些区域被认为对基因调控和肿瘤发生非常重要。通路分析显示，OLK和OSCC患者中差异甲基化的CpG位点具有相同的通路富集情况，其中大部分与肿瘤发生和癌症进展相关（如DNA修复、细胞周期和凋亡）。在本研究中，甲基化相关改变几乎影响OLK和OSCC细胞网络中的所有通路。OLK和OSCC在通路或基因方面具有相似的甲基化变化，表明在表观遗传学上它们可能具有相同的疾病进展分子基础。
