Aberrant DNA methylation of tumor‐related genes in oral rinse

Abstract

BACKGROUND:The early detection of oral squamous cell carcinoma (OSCC) is important, and a screening test with high sensitivity and specificity is urgently needed. Therefore, in this study, the authors investigated the methylation status of tumor-related genes with the objective of establishing a noninvasive method for the detection of OSCC. METHODS: Oral rinse samples were obtained from 34 patients with OSCC and from 24 healthy individuals (controls). The methylation status of 13 genes was determined by using methylation-specific polymerase chain reaction analysis and was quantified using a microchip electrophoresis system. Promoter methylation in each participant was screened by receiver operating characteristic analysis, and the utility of each gene's methylation status, alone and in combination with other genes, was evaluated as a tool for oral cancer detection. RESULTS: Eight of the 13 genes had significantly higher levels of DNA methylation in samples from patients with OSCC than in controls. The genes E-cadherin (ECAD), transmembrane protein with epidermal growth factor-like and 2 follistatin-like domains 2 (TMEFF2), retinoic acid receptor beta (RARb), and O-6 methylguanine DNA methyltransferase (MGMT) had high sensitivity (>75%) and specificity for the detection of oral cancer. OSCC was detected with 100% sensitivity and 87.5% specificity using a combination of ECAD, TMEFF2, RARb, and MGMT and with 97.1% sensitivity and 91.7% specificity using a combination of ECAD, TMEFF2, and MGMT. CONCLUSIONS: The aberrant methylation of a combination of marker genes present in oral rinse samples was used to detect OSCC with >90% sensitivity and specificity. The detection of methylated marker genes from oral rinse samples has great potential for the noninvasive detection of OSCC.

Diagnostic accuracy of DNA methylation for head and neck cancer varies by sample type and number of markers tested

“…Ten papers used saliva [9, 10, 12, 14, 17, 27, 29, 32, 50], sixteen papers used solid tissue [11, 15, 16, 18, 19, 23–26, 30, 31, 33–38, 40–46, 49], four papers used blood [21, 28, 31, 39], five papers used both solid tissue and saliva [8, 13, 22, 47, 51], and two papers used both solid tissue and blood (Table 1) [20, 33]. The studies evaluated the diagnostic power of methylation biomarkers as follows: thirty-five studies were based on a single gene [8, 12–14, 16–19, 21, 23, 25–28, 30, 32–51], two papers were based on multiple genes [9, 22] and seven papers were based on both single and multiple genes [10, 11, 15, 20, 24, 29, 31]. The details of methylated biomarkers and their diagnostic powers are shown in Supplementary Table 1.…”

Prognostic factors in oral and oropharyngeal cancer based on ultrastructural analysis and DNA methylation of the tumor and surgical margin

“…Ha and Califano [18] noticed that methylation of CDKN2A ranged from 0 to 85 % in oral cancer. Nagata et al found that methylation of four statistically selected genes including E-cadherin and RAR- β allows to detect oral cancer with 100 % sensitivity and 87.5 % specificity [43]. …”

Clinical implications of epigenetic regulation in oral cancer

“…Nagata et al (2012) demonstrated silencing of FHIT gene via hypermethylation in 79% oral cancers (n = 34) and 33% normal controls [37].…”