Aberrant DNA methylation of EDNRB, MGMT and TIMP3 gene promoters in saliva of head and neck carcinoma patients as a diagnostic tool.

Background: Differential DNA methylation in the promoter region of tumour suppressor genes leads to gene function silencing.

Materials And Methods: In this study, we aimed to evaluate the salivary promoter methylation of EDNRB, MGMT and TIMP3 genes in H&NC patients (n = 100), premalignant lesions patients (n = 25) and healthy controls (n = 50). Blood and saliva samples were collected from all three groups and 20 concomitant tumour tissues were collected from the H&NC patients. Probe-based Methylation-specific PCR (MSP) was performed to assess the relative quantification of methylation.

Results: Significant promoter hypermethylation was detected in all three genes between H&NC patients vs. healthy controls and premalignant lesion patients vs. healthy controls. Spearman correlation analysis showed, no significant association between methylation levels and clinicopathological characteristics of HNC patients while tobacco smoking was significantly related to EDNRB methylation in premalignant lesions. The receiver operating curve (ROC) generated for EDNRB, MGMT and TIMP3 genes from saliva samples was able to differentiate between cancer vs. healthy controls and premalignant vs. healthy controls. The combined diagnostic efficiency of the panel was higher than the genes singly. The combined sensitivity of EDNRB and TIMP3 increased to 92%.

Conclusion: This indicates that EDNRB and TIMP3 have potential value in clinical practice as effective diagnostic markers for H&NC using saliva samples.