Long interspersed nuclear element‐1 hypomethylation is a potential biomarker for the prediction of response to oral fluoropyrimidines in microsatellite stable and CpG island methylator phenotype‐negative colorectal cancer

摘要: We investigated the clinical value of methylation long interspersed nuclear element-1 (LINE-1) for prognosis colorectal cancer (CRC) and survival benefit from adjuvant chemotherapy with oral fluoropyrimidines. LINE-1 in tumor DNA was measured by quantitative methylation-specific PCR 155 samples stage II III CRC. The presence microsatellite instability CpG island methylator phenotype (CIMP) were assessed 131 stable/CIMP- cases selected analysis, which 77 patients had received postoperative CRC cell lines used to investigate possible mechanistic links between effects 5-fluorouracil (5-FU). High a marker better treated surgery alone. Patients low who survived longer than those alone, suggestive use In contrast, not observed high methylation. 5-FU showed increased expression mRNA. This associated upregulation phospho-histone H2A.X cells methylation, but 5-FU-mediated induction H2A.X, damage, inhibited knockdown LINE-1. These results suggest that is novel predictive fluoropyrimidines patients. finding could be important achieving personalized chemotherapy.