Department of Stomatology, China Resources and WISCO General Hospital.
Tohoku J Exp Med. 2023 May 26;260(2):109-117. doi: 10.1620/tjem.2023.J021. Epub 2023 Mar 16.
The modulation of gene expression via DNA methylation modifications is relevant to the pathogenesis of periodontitis. This study aimed at identifying novel biomarkers in gingival tissues from periodontitis by integrally analyzing methylation profiles and gene expression data. Differential gene expressions (DGEs) of dataset GSE106090 were obtained from the Gene Expression Omnibus (GEO) database for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. DNA methylation DGEs (DM-DGEs) were analyzed from dataset GSE173082. After integrating these two datasets, expressions of common genes were validated in gingival tissues from healthy controls and periodontitis patients by real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting. GO analysis of 748 upregulated and 847 downregulated DEGs from the GSE106090 dataset revealed that immune response-regulating signaling pathway, cell-cell junction and signaling receptor activator activity as the top enriched biological process (BP), cellular component (CC) and molecular function (MF), respectively. DEGs were mainly enriched in cytokine-cytokine receptor interaction, Ras signaling pathway, and chemokine signaling pathway. There was one up-regulated mRNA with hypo-methylated gene [ADAM28 (a disintegrin and metalloproteinase 28)] and one down-regulated mRNA with hyper-methylated gene [ADAMTSL3 (a disintegrin-like and metalloprotease domain with thrombospondin type I motifs-like-3)] after integrating GSE106090 and GSE173082 datasets. Increased ADAM28 expression was validated in gingival tissues from periodontitis patients as compared to the healthy controls with decreased ADAMTSL3 expression, which were correlated with disease stage. ADAM28 and ADAMTSL3 may act as novel biomarkers in gingival tissues from periodontitis by a comprehensive analysis of bioinformatics methods and executed validation.
通过 DNA 甲基化修饰来调节基因表达与牙周炎的发病机制有关。本研究旨在通过整合分析甲基化谱和基因表达数据,从牙周炎的牙龈组织中鉴定新的生物标志物。从基因表达综合数据库(GEO)数据库中获取数据集 GSE106090 的差异基因表达(DGE),用于基因本体论(GO)和京都基因与基因组百科全书(KEGG)途径分析。从数据集 GSE173082 分析 DNA 甲基化 DGE(DM-DGE)。整合这两个数据集后,通过实时定量聚合酶链反应(RT-qPCR)和 Western blot 验证了健康对照组和牙周炎患者牙龈组织中常见基因的表达。GSE106090 数据集上调的 748 个和下调的 847 个 DEG 的 GO 分析显示,免疫反应调节信号通路、细胞-细胞连接和信号受体激活活性分别是最富集的生物过程(BP)、细胞成分(CC)和分子功能(MF)。DEGs 主要富集在细胞因子-细胞因子受体相互作用、Ras 信号通路和趋化因子信号通路中。整合 GSE106090 和 GSE173082 数据集后,有一个上调的 mRNA 表现为低甲基化基因 [ADAM28(解整合素和金属蛋白酶 28)],一个下调的 mRNA 表现为高甲基化基因 [ADAMTSL3(解整合素样金属蛋白酶域与血小板反应蛋白 1 型基序样 3)]。与健康对照组相比,牙周炎患者的牙龈组织中 ADAM28 表达增加,而 ADAMTSL3 表达减少,这与疾病阶段有关。ADAM28 和 ADAMTSL3 可作为牙周炎牙龈组织中的新型生物标志物,通过生物信息学方法的综合分析和执行验证。