Hypomethylation of long interspersed element-1 is a prognostic factor in stage III or high-risk stage II colorectal cancers treated with adjuvant FOLFOX

Abstract

Background: Hypomethylation of Long intersperse element-1 (L1) is considered a surrogate marker for a decrease in methylcytosine content in tumor cells. Tumoral L1 hypomethylation correlates worse clinical outcome in patients with gastric cancer or esophageal cancer. However, it remains unclear whether low L1 methylation is a prognostic marker in colorectal cancers (CRCs). We aimed to elucidate whether tumoral L1 hypomethylation may have a prognostic role in CRCs treated with adjuvant FOLFOX.

Materials and methods: We analyzed a total of 427 resected cases of stage III or high-risk stage II CRC for their statuses in L1 methylation, CpG island methylator phenotype, microsatellite instability, and KRAS/BRAF mutation. L1 methylation was assayed by pyrosequencing.

Results: L1 hypomethylation was closely associated with nodal metastasis but did not show any association with age of onset, gender, tumor subsite, tumor differentiation, mucinous histology, lymphatic emboli, venous invasion, perineural invasion, T stage, and KRAS/BRAF mutation. Multivariate analysis revealed that L1 hypomethylation as well as mucinous histology, T stage, N stage, lymphatic emboli and KRAS mutation was an independent prognostic parameter heralding poor prognosis. Conclusion:Tumoral L1 hypomethylation correlated independently with poor prognosis in patients with resectable CRC treated with adjuvant FOLFOX.