title: TFAP2E hypermethylation was associated with survival advantage in patients with colorectal cancer.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Epidemiology, School of Public Health, Harbin Medical University, 157 Baojian Road, Harbin, 150086, Heilongjiang Province, People's Republic of China.
authors.forename: Zuo-Ming
authors.initials: ZM
authors.lastname: Zhang
authors.forename: Yibaina
authors.initials: Y
authors.lastname: Wang
authors.forename: Rong
authors.initials: R
authors.lastname: Huang
authors.forename: Yu-Peng
authors.initials: YP
authors.lastname: Liu
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.forename: Fu-Lan
authors.initials: FL
authors.lastname: Hu
authors.forename: Lin
authors.initials: L
authors.lastname: Zhu
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.forename: Bin-Bin
authors.initials: BB
authors.lastname: Cui
authors.forename: Xin-Shu
authors.initials: XS
authors.lastname: Dong
authors.forename: Ya-Shuang
authors.initials: YS
authors.lastname: Zhao
mesh_terms: D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D050656:Transcription Factor AP-2 / Q000235:genetics*
chemical_list: C493680:TFAP2E protein, human; D050656:Transcription Factor AP-2