Combinatory low methylation statuses of SAT-α and L1 are associated with shortened survival time in patients with advanced gastric cancer.

ABSTRACT

BACKGROUND: L1 and SAT-α are repetitive DNA elements that undergo demethylation in association with cancerization. Unlike L1 hypomethaylation, nothing is known regarding the prognostic implication of SAT-α hypomethylation alongside L1 hypomethaylaton in gastric cancers. METHODS: Formalin-fixed paraffin-embedded samples from 492 cases of advanced gastric cancer were analyzed to determine their L1 and SAT-α methylation status using pyrosequencing methylation assay. RESULTS: L1 and SAT-α methylation statuses were correlated with clinicopathological parameters, including survival. L1 or SAT-α methylation levels were lower in gastric cancers with venous invasion or nodal metastasis than those without. L1 methylation was lower in gastric cancers with lymphatic emboli than in those with no lymphatic emboli, but was higher in gastric cancers with perineural invasion than in those with no perineural invasion. Multivariate survival analysis revealed that both tumoral L1 and SAT-α hypomethylations were found to correlate independently with OS (HR = 1.477; 95% CI 1.079-2.021 and HR = 1.394; 95% CI 1.011-1.922, respectively) and RFS (HR = 1.477; 95% CI 1.090-2.001 and HR = 1.516; 95% CI 1.106-2.078, respectively). Combined L1 and SAT-α hypomethylation turned out to correlate independently with OS (HR = 2.003; 95% CI 1.268-3.164) and RFS (HR = 2.226; 95% CI 1.411-3.510). CONCLUSION: Not only tumoral L1 hypomethylation, but also tumoral SAT-α hypomethylation was found to be independent prognostic parameters in patients with advanced gastric cancer. SAT-α methylation status can be used to further divide gastric cancers with L1 hypomethylation into subsets of gastric cancers with better and worse prognosis.