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.
Keywords: bone morphogenetic protein 2; colorectal cancer; methylation; methylation-specific polymerase chain reaction; prognostic factor; tumor-suppressor gene.
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