High methylation rate of LMX1A, NKX6-1, PAX1, PTPRR, SOX1, and ZNF582 genes in cervical adenocarcinoma

Objective: This study aimed to investigate the status of DNA methylation of 6 genes, LMX1A, NKX6-1, PAX1, PTPRR, SOX1, and ZNF582, previously found from squamous cell carcinomas in adenocarcinomas (ACs) of the uterine cervix. Methods: We assessed the methylation status of these genes in 40 ACs, cervical scrapings from 23 ACs, and 67 normal control cervices by real-time quantitative methylation-specific polymerase chain reaction. The results were validated by bisulfite pyrosequencing. Results: The methylation levels of all the 6 genes in the ACs were significantly higher than those in normal cervical tissues, especially for PAX1, PTPRR, SOX1, and ZNF582. The odds ratios and 95% confidence intervals (CIs) of high methylation levels in PAX1, PTPRR, SOX1, and ZNF582 for the risk of developing an AC were 15.7 (95% CI, 7.0-40.6), 16.9 (95% CI, 7.6-43.0), 32.1 (95% CI, 12.1-124.3), and 25.4 (95% CI, 10.4-78.3), respectively (all P <0.001). The methylation indices of PAX1, PTPRR, SOX1, and ZNF582 recovered from scrapings of ACs were significantly higher than in normal controls. The odds ratios of these indices for the risk of developing an AC in PAX1, PTPRR, SOX1, and ZNF582 were 6.2 (95% CI, 2.6-15.4), 12.1(95% CI, 3.8-46.4), 6.2 (95% CI, 2.6-15.8), and 20.6 (95% CI, 6.9-77.5), respectively (all P <0.001). Conclusions: Cervical ACs carry aberrantly high methylation rates of PAX1, PTPRR, SOX1, and ZNF582Vcommonly methylated in squamous cell carcinomas - which might help for AC screening.