Background: Focal hypermethylation in promoter regions of tumor suppressor genes against the background of global hypomethylation is a
landmark of carcinogenesis. This study aimed to investigate the methylation status of retinoic acid receptor beta2 (RARb2) and long interspersed
nuclear elements (LINE‐1) in different stages of esophageal squamous cell carcinoma (ESCC).
Method: The tumor and adjacent normal esophageal tissues from 125 male ESCC patients who underwent primary surgery were analyzed for the
methylation status of RARb2 promoter and LINE‐1 through methylation‐specific polymerase chain reaction and pyrosequencing.
Results: RARb2 hypermethylation was detected in 20% of the tumor samples, but not in the normal counterparts. The methylation frequency of
LINE‐1 was significantly lower in the tumor than in the normal parts (median: 67.7% vs. 80%, P<0.0005). Ninety‐eight patients (78.4%) had both
RARb2 hypermethylation and LINE‐1 hypomethylation or either one. There was a trend toward higher risk of advanced T stage (P for trend¼0.05)
or lymph node metastasis (P for trend¼0.02) when more adverse gene methylation profiles were present.
Conclusion: Methylation status of RARb2 and LINE‐1 was related to the development and possibly the severity of ESCC.
