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posted on 2023-03-31, 19:44 authored by Oscar Murcia, Rodrigo Jover, Cecilia Egoavil, Lucia Perez-Carbonell, Miriam Juárez, Eva Hernández-Illán, Estefania Rojas, Cristina Alenda, Francesc Balaguer, Montserrat Andreu, Xavier Llor, Antoni Castells, C. Richard Boland, Ajay Goel Supplementary Figure 4. Epicolon I. Overall Survival Stage IV Patients: TFAP2E IHC Expression. Disease Free Survival Stage II and III Patients: TFAP2E IHC Expression. (A) Overall survival of patients with stage IV disease, according to TFAP2E expression status comparing staining scores 0 & 1 (Low expression) vs staining scores 2 & 3 (High expression;). (B) Overall survival of patients that received or did not receive (C) 5-FU based chemotherapy according to TFAP2E expression status. (D) Disease Free Survival (DFS) of patients with stage II and III CRC, according to TFAP2E expression status comparing staining scores 0 & 1 (Low expression) vs staining scores 2 & 3 (High expression) (E) DFS of stages II+III CRC patients that received or did not receive (F)) adjuvant chemotherapy according to TFAP2E expression status.
Funding
National Cancer Institute
NIH
Cancer Prevention Research Institute of Texas (CPRIT)
Baylor Sammons Cancer Center and Foundation
Baylor Research Institute
Instituto de Salud Carlos III
History
ARTICLE ABSTRACT
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.
