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. 2014 Dec;140(12):2119-27.
doi: 10.1007/s00432-014-1766-4. Epub 2014 Jul 6.

TFAP2E hypermethylation was associated with survival advantage in patients with colorectal cancer

Zuo-Ming Zhang  1 , Yibaina Wang, Rong Huang, Yu-Peng Liu, Xia Li, Fu-Lan Hu, Lin Zhu, Fan Wang, Bin-Bin Cui, Xin-Shu Dong, Ya-Shuang Zhao
Affiliations

TFAP2E hypermethylation was associated with survival advantage in patients with colorectal cancer

Zuo-Ming Zhang et al. J Cancer Res Clin Oncol. 2014 Dec.

Abstract

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.

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Conflict of interest statement

Ya-shuang Zhao had received two grants (NSFC 30972539 and 30671801) from National Natural Science Foundation of China for Priority Areas. The remaining authors did not have any relevant current or past conflict of interests or sources of funding.

Figures

Fig. 1
Fig. 1
Comparison of AP-2E methylation level in tumor and adjacent non-tumor tissue samples
Fig. 2
Fig. 2
Receiver operating characteristic (ROC) analysis on PM values of AP-2E from 78 patient-matched tumor and non-tumor tissues (a). The optimal PM cutoff value was identified according to the Youden index at 30.16 %, i.e., the point on the ROC curve farthest from the chance (b)
Fig. 3
Fig. 3
Kaplan–Meier curves for cumulative survival comparisons: between patients with AP-2E hypermethylation and hypomethylation (a); among patients with AP-2E hypermethylation-high, hypermethylation-low, and hypomethylation (b)
See this image and copyright information in PMC

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