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Review
. 2021 Jun 26;11(7):606.
doi: 10.3390/jpm11070606.

Salivary DNA Methylation as an Epigenetic Biomarker for Head and Neck Cancer. Part II: A Cancer Risk Meta-Analysis

Óscar Rapado-González  1   2   3 , Cristina Martínez-Reglero  4 , Ángel Salgado-Barreira  4 , María Arminda Santos  1   5 , Rafael López-López  3   6 , Ángel Díaz-Lagares  3   7 , María Mercedes Suárez-Cunqueiro  1   3   6
Affiliations
Review

Salivary DNA Methylation as an Epigenetic Biomarker for Head and Neck Cancer. Part II: A Cancer Risk Meta-Analysis

Óscar Rapado-González et al. J Pers Med. .

Abstract

Aberrant methylation of tumor suppressor genes has been reported as an important epigenetic silencer in head and neck cancer (HNC) pathogenesis. Here, we performed a comprehensive meta-analysis to evaluate the overall and specific impact of salivary gene promoter methylation on HNC risk. The methodological quality was assessed using the Newcastle-Ottawa scale (NOS). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association and Egger's and Begg's tests were applied to detect publication bias. The frequency of salivary DNA promoter methylation was significantly higher in HNC patients than in healthy controls (OR: 8.34 (95% CI = 6.10-11.39; p < 0.01). The pooled ORs showed a significant association between specific tumor-related genes and HNC risk: p16 (3.75; 95% CI = 2.51-5.60), MGMT (5.72; 95% CI = 3.00-10.91), DAPK (5.34; 95% CI = 2.18-13.10), TIMP3 (3.42; 95% CI = 1.99-5.88), and RASSF1A (7.69; 95% CI = 3.88-15.23). Overall, our meta-analysis provides precise evidence on the association between salivary DNA promoter hypermethylation and HNC risk. Thus, detection of promoter DNA methylation in saliva is a potential biomarker for predicting HNC risk.

Keywords: DNA methylation; biomarkers; epigenetics; head and neck cancer; liquid biopsy; meta-analysis; saliva.

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Conflict of interest statement

R.L.-L. reports other from Nasasbiotech, during the conduct of the study; grants and personal fees from Roche, grants and personal fees from Merck, personal fees from AstraZeneca, personal fees from Bayer, personal fees and non-financial support from BMS, personal fees from Pharmamar, personal fees from Leo, outside the submitted work. The rest of the authors have nothing to disclose. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Forest plot for the association between salivary DNA promoter hypermethylation and the HNC risk. The squares represent the ORs for individual studies. Bars represent the 95% CIs. The center of the diamond represents the summary effect size.
Figure 2
Figure 2
Forest plot for the association between p16 promoter hypermethylation and HNC risk. The squares represent the ORs for individual studies. Bars represent the 95% CIs. The center of the diamond represents the summary effect size.
Figure 3
Figure 3
Forest plot for the association between MGMT promoter hypermethylation and HNC risk. The squares represent the ORs for individual studies. Bars represent the 95% CIs. The center of the diamond represents the summary effect size.
Figure 4
Figure 4
Forest plot for the association between DAPK promoter hypermethylation and HNC risk. The squares represent the ORs for individual studies. Bars represent the 95% CIs. The center of the diamond represents the summary effect size.
Figure 5
Figure 5
Forest plot for the association between TIMP3 promoter hypermethylation and HNC risk. The squares represent the ORs for individual studies. Bars represent the 95% CIs. The center of the diamond represents the summary effect size.
Figure 6
Figure 6
Forest plot for the association between RASSF1A promoter hypermethylation and the HNC risk. The squares represent the ORs for individual studies. Bars represent the 95% CIs. The center of the diamond represents the summary effect size.
Figure 7
Figure 7
Forest plot for the association between APC promoter hypermethylation and HNC risk. The squares represent the ORs for individual studies. Bars represent the 95% CIs. The center of the diamond represents the summary effect size.
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