Purpose: Hypermethylation of TFAP2E (AP-2E) is associated with the chemotherapy-resistant in patients with colorectal cancer (CRC), but its implications on prognosis directly remain unknown. This study was aimed to investigate the role of AP-2E methylation status and other clinicopathologic parameters as predictors of prognosis.
Methods: We detected the methylation status of AP-2E in tumor and adjacent non-tumor tissues from 311 sporadic CRC patients by methylation-sensitive high-resolution melting analysis. Log-rank tests and multivariate Cox analyses were performed to evaluate the role of AP-2E methylation status and other clinicopathologic parameters as predictors of prognosis.
Results: Hypermethylation of AP-2E was detected in 61 % (190/311) tumor tissues. It occurred more frequently in tumors in earlier stages (I/II; P = 0.02), lower levels of tumor invasion (T1-T3; P = 0.04), fewer lymph nodes involved (N0; P < 0.01), and higher histologic grades (G1/G2; P < 0.01). The overall 5-year survival rates in hypermethylation and hypomethylation group were 76.91 and 47.17 % (P < 0.0001), respectively. AP-2E hypermethylation was significantly associated with a favorable clinical outcome with a hazard ratio of 0.486 (95 % CI 0.342-0.692, P < 0.0001) after controlling for age, gender, tumor location, histologic type, TNM staging, and histologic grade.
Conclusions: AP-2E was frequently hypermethylated in tumors from patients with CRC. Aberrant hypermethylation of AP-2E occurred more frequently in tumors with earlier stages, lower levels of tumor invasion, fewer lymph nodes involved, and higher histologic grades. AP-2E hypermethylation might be an independent predictor of survival advantage in patients with CRC.