CDKN2A methylation in esophageal cancer: a meta-analysis

CDKN2A is a tumor suppressor gene and is frequently inactivated in human cancers by hypermethylation of its promoter. However, the role and diagnostic value of CDKN2A methylation in esophageal cancer (EC) remains controversial. Therefore, we performed a meta-analysis, including data from 42 articles (2656 ECs, 612 precancerous lesions, and 2367 controls). A significant increase in the frequency of CDKN2A methylation was identified during EC carcinogenesis: cancer vs. controls, odds ratio (OR) = 12.60 (95 % CI, 8.90-17.85); cancer vs. precancerous lesions, OR = 2.89 (95% CI, 2.20-3.79); and precancerous lesions vs. controls, OR = 7.38, 95% (CI, 4.31-12.66). CDKN2A promoter methylation was associated with EC tumor grade (OR = 1.79; 95% CI, 1.20-2.67) and clinical stage (OR = 2.56; 95% CI, 1.33-4.92). Additionally, the sensitivity, specificity, and area under the summary receiver operating characteristic curve (AUC) for diagnosis of EC based on CDKN2A methylation were 0.52 (95% CI, 0.44-0.59), 0.96 (95% CI, 0.93-0.98), and 0.83 (95% CI, 0.79-0.86), respectively. AUCs for blood and tissue sample subgroups were 0.90 and 0.82, respectively. Our findings indicate that CDKN2A methylation has a vital role in EC tumorigenesis and could be a biomarker for early diagnosis of EC.