Methylation of bone morphogenetic protein 2 is associated with poor prognosis in colorectal cancer

The present study investigated aberrant methylation in colorectal cancer (CRC) and its impact on characteristics and prognosis of patients with CRC. Bone morphogenetic protein 2 (BMP2) was identified as a target gene in oligonucleotide microarray expression profiling in a previous study. Subsequently, the BMP2 methylation status was assessed in 498 patients with stage I-III CRC using methylation-specific polymerase chain reaction, and the association between BMP2 methylation status, patient characteristics and prognosis was assessed. BMP2 methylation was observed in 302/498 (60.6%) patients and was associated with positive lymph nodes and venous invasion (P<0.05). In the stage III subgroup, overall survival (OS) was significantly worse in the methylated BMP2 group compared with in the unmethylated BMP2 group (P=0.012). BMP2 methylation was identified as an independent factor for poor OS in stage III patients (P=0.041). Notably, in the left-sided stage III CRC subgroup, relapse-free survival and OS were significantly worse in the methylated BMP2 group than in the unmethylated group (P=0.048 and P=0.031, respectively). In conclusion, DNA hypermethylation of BMP2 was a poor prognostic factor in patients with stage III disease, particularly in those with left-sided stage III CRC. BMP2 methylation may be a biomarker for prognosis prediction and treatment decision-making.