High-risk oral leukoplakia is associated with aberrant promoter methylation of multiple genes.
High-risk oral leukoplakia is associated with aberrant promoter methylation of multiple genes.
复制标题
DOI：
10.1186/s12885-016-2371-5
复制
发表时间：
2016-06-03
期刊：
影响因子：
3.8
通讯作者：
Takato T
中科院分区：
文献类型：
--
作者：
Abe M;Yamashita S;Mori Y;Abe T;Saijo H;Hoshi K;Ushijima T;Takato T
口腔鳞状细胞癌的早期诊断是改善患者预后和提高生活质量的迫切需要。口腔白斑病是口腔内最常见的癌前病变，常发生于口腔鳞状细胞癌之前。特别是，已知具有异型增生的OL具有高的恶性转化风险。在这里，我们寻找高风险OL的启动子甲基化特征。为了鉴定甲基化沉默的基因，在两种OSCC细胞系（Ca 9 -22和HSC-2）中进行甲基化DNA免疫沉淀（MeDIP）-CpG岛（CGI）微阵列分析和用去甲基化剂处理后的表达微阵列分析的组合分析。甲基化特异性PCR检测各基因的甲基化状态。在Ca 9 -22或HSC-2中总共鉴定出52个基因作为甲基化沉默基因的候选者。随机选择进行进一步分析的15个基因中，有13个基因的启动子区在5个细胞系中的一个或多个中被证实甲基化。在26例口腔鳞癌组织中，TSPYL 5、EGFLAM、CLDN 11、NKX 2 -3、RBP 4、CMTM 3、TRPC 4和MAP 6等13个基因中有8个发生甲基化。在OL组织（n = 24），7的8个基因，除了EGFLAM，被发现在其启动子区甲基化。有异型增生的OLs中甲基化基因的数量显著高于无异型增生的OLs（p < 0.0001）。恶性转化高风险的OL与多个基因的异常启动子甲基化相关。本文的在线版本（doi：10.1186/s12885-016-2371-5）包含补充材料，可供授权用户使用。
Early detection of oral squamous cell carcinomas (OSCCs) is urgently needed to improve the prognosis and quality of life (QOL) of patients. Oral leukoplakias (OLs), known as the most common premalignant lesions in the oral cavity, often precede OSCCs. Especially, OLs with dysplasia are known to have a high risk of malignant transformation. Here, we searched for the promoter methylation characteristic of high-risk OLs. To identify methylation-silenced genes, a combined analysis of methylated DNA immunoprecipitation (MeDIP) − CpG island (CGI) microarray analysis and expression microarray analysis after treatment with a demethylating agent was performed in two OSCC cell lines (Ca9–22 and HSC-2). The methylation statuses of each gene were examined by methylation-specific PCR. A total of 52 genes were identified as candidates for methylation-silenced genes in Ca9-22 or HSC-2. The promoter regions of 13 genes among the 15 genes randomly selected for further analysis were confirmed to be methylated in one or more of five cell lines. In OSCC tissues (n = 26), 8 of the 13 genes, TSPYL5, EGFLAM, CLDN11, NKX2-3, RBP4, CMTM3, TRPC4, and MAP6, were methylated. In OL tissues (n = 24), seven of the eight genes, except for EGFLAM, were found to be methylated in their promoter regions. There were significantly greater numbers of methylated genes in OLs with dysplasia than in those without dysplasia (p < 0.0001). OLs at high risk for malignant transformation were associated with aberrant promoter methylation of multiple genes. The online version of this article (doi:10.1186/s12885-016-2371-5) contains supplementary material, which is available to authorized users.