» Articles » PMID: 31013839

Promoter Hypermethylation of Tumor-Suppressor Genes , and in Salivary DNA As a Quadruple Biomarker Panel for Early Detection of Oral and Oropharyngeal Cancers

Overview
Journal Biomolecules
Publisher MDPI
Date 2019 Apr 25
PMID 31013839
Citations 30
Authors
Affiliations
Soon will be listed here.
Abstract

Silencing of tumor-suppressor genes (TSGs) by DNA promoter hypermethylation is an early event in carcinogenesis; hence, TSGs may serve as early tumor biomarkers. We determined the promoter methylation levels of , , , and TSGs in salivary DNA from oral cancer (OC) and oropharyngeal cancer (OPC) patients, using methylation-specific PCR coupled with densitometry analysis. We assessed the association between DNA methylation of individual TSGs with OC and OPC risk factors. The performance and the clinical validity of this quadruple-methylation marker panel were evaluated in discriminating OC and OPC patients from healthy controls using the CombiROC web tool. Our study reports that , , and TSGs were significantly hypermethylated in OC and OPC cases compared to healthy controls. DNA methylation levels of TSGs were significantly augmented by smoking, alcohol use, and betel quid chewing, indicating the fact that frequent exposure to risk factors may drive oral and oropharyngeal carcinogenesis through TSG promoter hypermethylation. Also, this quadruple-methylation marker panel of , , , and TSGs demonstrated excellent diagnostic accuracy in the early detection of OC at 91.7% sensitivity and 92.3% specificity and of OPC at 99.8% sensitivity and 92.1% specificity from healthy controls.

Citing Articles

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

Shekhawat J, Sharma J, Choudhury B, Chugh A, Purohit P, Sharma P Mol Biol Rep. 2025; 52(1):152.

PMID: 39847241 DOI: 10.1007/s11033-025-10250-7.


The Role of Oral Biomarkers in the Assessment of Noncommunicable Diseases.

Saenz-Ravello G, Hernandez M, Baeza M, Hernandez-Rios P Diagnostics (Basel). 2025; 15(1.

PMID: 39795606 PMC: 11719684. DOI: 10.3390/diagnostics15010078.


Salivary biomarkers: a promising approach for predicting immunotherapy response in head and neck cancers.

Nejat Dehkordi A, Maddahi M, Vafa P, Ebrahimi N, Aref A Clin Transl Oncol. 2024; .

PMID: 39377974 DOI: 10.1007/s12094-024-03742-8.


Moesin contributes to heat shock gene response through direct binding to the Med15 subunit of the Mediator complex in the nucleus.

Kristo I, Kovacs Z, Szabo A, Borkuti P, Graf A, Santa A Open Biol. 2024; 14(10):240110.

PMID: 39353569 PMC: 11444770. DOI: 10.1098/rsob.240110.


Salivary biomarkers in non-invasive oral cancer diagnostics: a comprehensive review.

Vats R, Yadav P, Bano A, Wadhwa S, Bhardwaj R J Appl Oral Sci. 2024; 32:e20240151.

PMID: 39258715 PMC: 11464085. DOI: 10.1590/1678-7757-2024-0151.


References
1.
Scully C, Bedi R . Ethnicity and oral cancer. Lancet Oncol. 2002; 1(1):37-42. DOI: 10.1016/S1470-2045(00)00008-5. View

2.
Al-Kaabi A, van Bockel L, Pothen A, Willems S . p16INK4A and p14ARF gene promoter hypermethylation as prognostic biomarker in oral and oropharyngeal squamous cell carcinoma: a review. Dis Markers. 2014; 2014:260549. PMC: 3997957. DOI: 10.1155/2014/260549. View

3.
Gunasekera S, Perera K, Fernando C, Udagama P . A shifting paradigm in the aetiology of oral and pharyngeal cancer in Sri Lanka: a case-control study providing serologic evidence for the role of oncogenic HPV types 16 and 18. Infect Agent Cancer. 2015; 10:12. PMC: 4407420. DOI: 10.1186/s13027-015-0007-z. View

4.
Topkas E, Keith P, Dimeski G, Cooper-White J, Punyadeera C . Evaluation of saliva collection devices for the analysis of proteins. Clin Chim Acta. 2012; 413(13-14):1066-70. DOI: 10.1016/j.cca.2012.02.020. View

5.
Siegel E, Riggs B, Delmas A, Koch A, Hakam A, Brown K . Quantitative DNA methylation analysis of candidate genes in cervical cancer. PLoS One. 2015; 10(3):e0122495. PMC: 4380427. DOI: 10.1371/journal.pone.0122495. View