Abstract
BackgroundEarly 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.MethodsTo 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.ResultsA 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).ConclusionsOLs at high risk for malignant transformation were associated with aberrant promoter methylation of multiple genes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2371-5) contains supplementary material, which is available to authorized users.
Highlights
Detection of oral squamous cell carcinomas (OSCCs) is urgently needed to improve the prognosis and quality of life (QOL) of patients
In the Ca9–22 cell line, the methylated DNA immunoprecipitation (MeDIP) − CpG island (CGI) microarray showed that 797 promoter CGIs were hypermethylated, and the expression microarray data showed that the expression levels of 675 genes were upregulated three-fold or more after 5-aza-dC treatment
In the HSC-2 cell line, the MeDIP − CGI microarray showed that 513 promoter CGIs were hypermethylated, and the expression microarray data showed that the expression levels of 212 genes were upregulated three-fold or more after 5-aza-dC treatment
Summary
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. We searched for the promoter methylation characteristic of high-risk OLs. Oral cancer is a major public health problem worldwide, and OSCC is the most common type of oral cancer. Early and accurate detection of OSCCs is important not. For the early detection of OSCCs, a finding of oral premalignant lesions with high-risk malignant transformation is important. The molecular mechanism underlying malignant transformation of OLs has not been elucidated yet, and molecular markers to identify patients at higher risk of developing OSCC have not been isolated [9]
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