Methylation status of the and promoter in cell-free circulating DNA and its prognostic role in patients with colorectal cancer.

DNA methylation is the most frequent epigenetic alteration. Using methylation-specific polymerase chain reaction (MSP), the methylation status of the adenomatous polyposis coli () and Ras association domain family 1 isoform A () genes was examined in cell-free circulating DNA from 155 plasma samples obtained from patients with early and advanced colorectal cancer (CRC). and hypermethylation was frequently observed in both early and advanced disease, and was significantly associated with a poorer disease outcome. The methylation status of the and promoters was investigated in cell-free DNA of patients with CRC. Using MSP, the promoter methylation status of and was examined in 155 blood samples obtained from patients with CRC, 88 of whom had operable CRC (oCRC) and 67 had metastatic CRC (mCRC). The frequency of methylation in patients with oCRC was 33%. Methylated promoter was significantly associated with older age (P=0.012), higher stage (P=0.014) and methylated status (P=0.050). The frequency of methylation in patients with mCRC was 53.7%. In these patients, methylation was significantly associated with methylated status (P=0.016). The frequency of methylation in patients with oCRC was 25%. Methylated in oCRC was significantly associated with higher stage (P=0.021). The frequency of methylation in mCRC was 44.8%. Methylated in mCRC was associated with moderate differentiation (P=0.012), high levels of carcinoembryonic antigen (P=0.023) and methylated status (P=0.016). Patients with an unmethylated gene had better survival in both early (81±5 vs. 27±4 months, P<0.001) and advanced disease (37±7 vs. 15±3 months, P<0.001), compared with patients with methylated . Patients with an unmethylated gene had better survival in both early (71±6 vs. 46±8 months, P<0.001) and advanced disease (28±4 vs. 16±3 months, P<0.001) than patients with methylated . The observed significant correlations between and promoter methylation status and survival may be indicative of a prognostic role for these genes in CRC, which requires additional testing in larger studies.