Role of methylation in esophageal cancer carcinogenesis and its clinical significance.

The mutL homolog-1 () is a DNA mismatch repair gene and has been reported to be frequently methylated in numerous cancers. However, the association between methylation and esophageal cancer (EC), as well as its clinical significance, remains unclear. Hence, we conducted a systematic meta-analysis based on 19 articles (including 1384 ECs, 345 premalignant lesions, and 1244 healthy controls). Our analysis revealed that the frequency of methylation was significantly elevated during EC carcinogenesis. In addition, we observed that promoter methylation was associated with age (odds ratio [OR]=1.79; 95% CI =1.20-2.66), advanced tumor grade (OR=3.7; 95% CI =2.37-5.77), lymph node metastasis (OR=2.65; 95% CI =1.81-3.88), distant metastasis (OR=7.60; 95% CI =1.23-47.19), advanced clinical stage (OR=4.46; 95% CI =2.88-6.91), and poor prognosis in EC patients (hazard ratio =1.64, 95% CI =1.00-2.69). The pooled sensitivity, specificity, and area under the curve of methylation in EC patients versus healthy individuals were 0.15, 0.99, and 0.77, respectively. Our findings indicate that methylation is involved in the carcinogenesis, progression, and metastasis of EC. Moreover, methylated could be a potential diagnostic and prognostic biomarker for EC.