Salivary DNA Methylation as an Epigenetic Biomarker for Head and Neck Cancer. Part I: A Diagnostic Accuracy Meta-Analysis

Abstract

DNA hypermethylation is an important epigenetic mechanism for gene expression inactivation in head and neck cancer (HNC). Saliva has emerged as a novel liquid biopsy representing a potential source of biomarkers. We performed a comprehensive meta-analysis to evaluate the overall diagnostic accuracy of salivary DNA methylation for detecting HNC. PubMed EMBASE, Web of Science, LILACS, and the Cochrane Library were searched. Study quality was assessed by the Quality Assessment for Studies of Diagnostic Accuracy-2, and sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (dOR), and their corresponding 95% confidence intervals (CIs) were calculated using a bivariate random-effect meta-analysis model. Meta-regression and subgroup analyses were performed to assess heterogeneity. Eighty-four study units from 18 articles with 8368 subjects were included. The pooled sensitivity and specificity of salivary DNA methylation were 0.39 and 0.87, respectively, while PLR and NLR were 3.68 and 0.63, respectively. The overall area under the curve (AUC) was 0.81 and the dOR was 8.34. The combination of methylated genes showed higher diagnostic accuracy (AUC, 0.92 and dOR, 36.97) than individual gene analysis (AUC, 0.77 and dOR, 6.02). These findings provide evidence regarding the potential clinical application of salivary DNA methylation for HNC diagnosis.

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

“…The outcomes of meta-regression analysis showed that sample type ( p = 0.128), sample size ( p = 0.349), and DNA methylation method ( p = 0.275) were not significant sources of heterogeneity. However, anatomic tumor location ( p = 0.002) and gene profiling ( p < 0.001) were, in fact, potential sources of heterogeneity in this study ( Table S1 —see Part I) [ 13 ]. As shown in Table S2 , significant heterogeneity was found in all subgroups.…”

Salivary biomarkers in breast cancer diagnosis: A systematic review and diagnostic meta‐analysis

“…Some studies have reported that biomarker accuracy in the Chinese population is different from other countries. 71,72 Although a number of systematic reviews have examined the utility of saliva in the diagnosis of oral, head, and neck malignancies, [73][74][75][76][77][78][79] limited review studies on the use of salivary biomarkers for diagnosis of distant cancers, especially BC are available. 54 To the best of our knowledge, this is the first systematic review and meta-analysis evaluating the potential of salivary biomarkers in the diagnosis of BC.…”

Liquid biopsies based on DNA methylation as biomarkers for the detection and prognosis of lung cancer

“…Previous studies have suggested that some methylation profiles in saliva were similar to those in tissue [ 135 ]. Moreover, saliva can be collected in a noninvasive, cost-effective, fast, and reliable way [ 135 , 136 ]. Therefore, salivary biomarkers can be applied to early detection, prognosis, and therapeutic effect response of cancer.…”

“…In recent years, saliva-based liquid biopsy for cancer has received much attention [127][128][129][130][131][132]. Analyzing components of saliva can reflect genomic and epigenomic alterations involved in physiological and pathological processes, and thus reflecting a person's physical conditions [133][134][135]. Previous studies have suggested that some methylation profiles in saliva were similar to those in tissue [135].…”

“…Analyzing components of saliva can reflect genomic and epigenomic alterations involved in physiological and pathological processes, and thus reflecting a person's physical conditions [133][134][135]. Previous studies have suggested that some methylation profiles in saliva were similar to those in tissue [135]. Moreover, saliva can be collected in a noninvasive, cost-effective, fast, and reliable way [135,136].…”