A minimal DNA 5-methylcytosine signature of oral tongue squamous cell carcinoma links altered methylation with tumor characteristics

Oral tongue squamous cell carcinomas (OTSCC) are a homogenous group of aggressive tumors in the head and neck region that spread early to lymph nodes and have a higher incidence of regional failure. Additionally, there is a rising incidence of oral tongue cancer among younger population. Studies on functional DNA methylation changes linked with altered gene expression are important towards understanding of tumor development and metastasis. Such studies may provide insights into biomarkers linked with viral infection, tumor metastasis and patient survival in OTSCC. We performed genome-wide methylation analysis of tumors (<i>N</i> = 52) and correlated altered methylation with differential gene expression. The minimal tumor-specific DNA methylation signature identified genes near 16 different differentially methylated regions (DMRs), which were validated using data from the cancer genome atlas (TCGA) cohort. In our cohort, hypermethylation of the microRNA <i>MiR-10B</i> was significantly associated with the differential expression of its target genes <i>NR4A3</i> and <i>BCL2L11</i> (<i>P</i> = 0.0125 and <i>P</i> = 0.014 respectively), which was inversely correlated with disease-free survival (<i>P</i> = 9E-15 and <i>P </i>= 2E-15 respectively) in patients. We found differential methylation in <i>FUT3</i>,<i> TRIM5</i>, <i>TSPAN7</i>,<i> MAP3K8,</i> <i>RPS6KA2, SLC9A9 </i>and<i> NPAS3</i> genes to be predictive of certain clinical and epidemiological parameters. <b>Implications</b>: Our study identified a functional minimal methylation signature in oral tongue tumors and linked various signatures with risk habits, clinical and epidemiological parameters. Down-regulation of <i>NR4A3 </i>and its correlation with patient survival makes it a potential target for therapeutic intervention in oral tongue tumors. Data from the current study are deposited in the NCBI Geo database (Accession number GSE75540).