The diagnostic value of methylated DNA in laryngeal squamous cell carcinoma: Meta-analysis

Abstract

Background: Laryngeal squamous cell carcinoma (LSCC) is the second most common head and neck squamous cell carcinoma (HNSCC). Although it is recognized that early detection of LSCC is a good prognostic factor for the patients, patients usually present late and with high recurrence rate. The use of methylated DNA is considered as a good surrogate marker of cancer as each cancer type has specific methylation phenotype which is distinguishable from the normal counterparts. Although intensive efforts had been made on clinical use of methylation markers for cancer surveillance, the use of methylated DNA in differentiating LSCC patients remains unclear. Methods: Pooled sensitivity and specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and the summary estimates of diagnostic odds ratio (DOR) were elucidated from the synthesized data. The diagnostic performance of methylated DNA markers was assessed by summary receiver operating curve (SROC) using random-effects models. Publication bias was examined with the use of Deeks' funnel plot. Results: Data from 27 studies containing 2262 tissue samples were extracted. Among the 16 methylated DNA markers, which had been applied on the LSCC, 6 of the 16 (37.5%) methylated genes are statistically significant (p < 0.05) in differentiating the cancerous tissues from the normal counterparts. The combined sensitivity and specificity were 0.62(95%CI:0.46-0.76) and 0.91(95%CI:0.79-0.97); the pooled PLR and NLR were 7.2 (95%CI:2.5-20.4) and 0.42(95%CI:0.27-0.65); the DOR were 17 (95%CI:4-69). Conclusion: In view of the property that aberrant DNA methylation occurs in the early developmental stages of LSCC, methylation markers are good for the detection of visually undetectable cases in the LSCC tissues. However, based on the current markers panel, the accuracy of methylated DNA markers are not satisfactory for clinical use. Identification of novel methylated markers with higher sensitivity and specificity is warranted.