TFAP2E Methylation and Expression Status Does Not Predict Response to 5-FU-based Chemotherapy in Colorectal Cancer.
Oscar MurciaRodrigo JoverCecilia M EgoavilLucia Perez-CarbonellMiriam JuárezEva Hernández-IllánEstefania RojasCristina AlendaFrancesc BalaguerMontserrat AndreuXavier LlorAntoni CastellsC Richard BolandAjay GoelPublished in: Clinical cancer research : an official journal of the American Association for Cancer Research (2018)
Purpose: A recent study reported that 5-fluorouracil (5-FU)-based chemotherapy is less effective in treating patients with advanced colorectal cancer demonstrating hypermethylation of the TFAP2E gene. The aim of our study was to confirm and validate these findings in large, uniformly treated, well-characterized patient cohorts.Experimental Design: Two cohorts of 783 patients with colorectal cancer: 532 from a population-based, multicenter cohort (EPICOLON I) and 251 patients from a clinic-based trial were used to study the effectiveness of TFAP2E methylation and expression as a predictor of response of colorectal cancer patients to 5-FU-based chemotherapy. DNA methylation status of the TFAP2E gene in patients with colorectal cancer was assessed by quantitative bisulfite pyrosequencing analysis. IHC analysis of the TFAP2E protein expression was also performed.Results: Correlation between TFAP2E methylation status and IHC staining was performed in 607 colorectal cancer samples. Among 357 hypermethylated tumors, only 141 (39.6%) exhibited loss of protein expression. Survival was not affected by TFAP2E hypermethylation in stage IV patients [HR, 1.21; 95% confidence interval (CI), 0.79-1.87; log-rank P = 0.6]. In stage II-III cases, disease-free survival was not influenced by TFAP2E hypermethylation status in 5-FU-treated (HR, 0.91; 95% CI, 0.52-1.59; log-rank P = 0.9) as well as in nontreated patients (HR, 0.88; 95% CI, 0.5-1.54; log-rank P = 0.7).Conclusions:TFAP2E hypermethylation does not correlate with loss of its protein expression. Our large, systematic, and comprehensive study indicates that TFAP2E methylation and expression may not play a major role in predicting response to 5-FU-based chemotherapy in patients with colorectal cancer. Clin Cancer Res; 24(12); 2820-7. ©2018 AACR.
Keyphrases
- dna methylation
- end stage renal disease
- genome wide
- newly diagnosed
- ejection fraction
- chronic kidney disease
- poor prognosis
- free survival
- randomized controlled trial
- prognostic factors
- binding protein
- locally advanced
- clinical trial
- young adults
- study protocol
- radiation therapy
- cross sectional
- open label
- case report
- data analysis