PURPOSE: This study was designed to determine whether DNA methylation biomarkers are associated with recurrence and survival in colon cancer patients. EXPERIMENTAL DESIGN: A retrospective analysis of 82 patients who received curative surgical resection for American Joint Committee on Cancer (AJCC) high-risk stage II or III colon cancer (1999-2007) was conducted. DNA methylation status was quantitatively evaluated by the pyrosequencing method. We preselected three tumor suppressor genes and one locus of interest; CHFR, ID4, RECK, and MINT1. Mean methylation levels of multiple CpG sites in the promoter regions were used for analysis; 15% or more was defined as methylation positive. The association of recurrence-free survival (RFS) and overall survival (OS) with methylation status was analyzed by the log-rank test, Kaplan-Meier method, and Cox proportional hazards model. RESULTS: Methylation levels of ID4, MINT1, and RECK did not correlate with RFS or OS. CHFR was methylation positive in 63% patients. When methylation status was dichotomized (negative or low: <30%, high: ≥30%), patients with CHFR methylation-high (44%) had worse RFS (P = 0.006) and reduced OS (P = 0.069). When stratified by stage, CHFR methylation-high was associated with reduced RFS (P = 0.004) and OS (P = 0.010) in stage III patients. CHFR methylation-high was commonly associated with N2 disease (P = 0.04) and proximal tumors (P = 0.002). Multivariate analysis indicated AJCC T4 disease and CHFR methylation-high (P = 0.001 and P = 0.015, respectively) were independent predictors for recurrence. CONCLUSIONS: The extent of CHFR promoter methylation correlates with RFS, indicating it is a promising epigenetic marker for recurrence.
PURPOSE: This study was designed to determine whether DNA methylation biomarkers are associated with recurrence and survival in colon cancerpatients. EXPERIMENTAL DESIGN: A retrospective analysis of 82 patients who received curative surgical resection for American Joint Committee on Cancer (AJCC) high-risk stage II or III colon cancer (1999-2007) was conducted. DNA methylation status was quantitatively evaluated by the pyrosequencing method. We preselected three tumor suppressor genes and one locus of interest; CHFR, ID4, RECK, and MINT1. Mean methylation levels of multiple CpG sites in the promoter regions were used for analysis; 15% or more was defined as methylation positive. The association of recurrence-free survival (RFS) and overall survival (OS) with methylation status was analyzed by the log-rank test, Kaplan-Meier method, and Cox proportional hazards model. RESULTS: Methylation levels of ID4, MINT1, and RECK did not correlate with RFS or OS. CHFR was methylation positive in 63% patients. When methylation status was dichotomized (negative or low: <30%, high: ≥30%), patients with CHFR methylation-high (44%) had worse RFS (P = 0.006) and reduced OS (P = 0.069). When stratified by stage, CHFR methylation-high was associated with reduced RFS (P = 0.004) and OS (P = 0.010) in stage III patients. CHFR methylation-high was commonly associated with N2 disease (P = 0.04) and proximal tumors (P = 0.002). Multivariate analysis indicated AJCC T4 disease and CHFR methylation-high (P = 0.001 and P = 0.015, respectively) were independent predictors for recurrence. CONCLUSIONS: The extent of CHFR promoter methylation correlates with RFS, indicating it is a promising epigenetic marker for recurrence.
Authors: Yan Y Sanders; Namasivayam Ambalavanan; Brian Halloran; Xiangyu Zhang; Hui Liu; David K Crossman; Molly Bray; Kui Zhang; Victor J Thannickal; James S Hagood Journal: Am J Respir Crit Care Med Date: 2012-06-14 Impact factor: 21.405
Authors: Muriel X G Draht; Kim M Smits; Benjamin Tournier; Valerie Jooste; Caroline Chapusot; Beatriz Carvalho; Arjen H G Cleven; Sarah Derks; Kim A D Wouters; Eric J T Belt; Hein B A C Stockmann; Herman Bril; Matty P Weijenberg; Piet A van den Brandt; Adriaan P de Bruïne; James G Herman; Gerrit A Meijer; Françoise Piard; Veerle Melotte; Manon van Engeland Journal: Mol Oncol Date: 2014-02-02 Impact factor: 6.603
Authors: Yu Imamura; Teppei Morikawa; Xiaoyun Liao; Paul Lochhead; Aya Kuchiba; Mai Yamauchi; Zhi Rong Qian; Reiko Nishihara; Jeffrey A Meyerhardt; Kevin M Haigis; Charles S Fuchs; Shuji Ogino Journal: Clin Cancer Res Date: 2012-07-02 Impact factor: 12.531
Authors: Lorraine Pelosof; Sashidhar R Yerram; Nita Ahuja; Andrew Delmas; Ludmila Danilova; James G Herman; Nilofer S Azad Journal: Int J Cancer Date: 2013-08-24 Impact factor: 7.396
Authors: Xiaoyun Liao; Teppei Morikawa; Paul Lochhead; Yu Imamura; Aya Kuchiba; Mai Yamauchi; Katsuhiko Nosho; Zhi Rong Qian; Reiko Nishihara; Jeffrey A Meyerhardt; Charles S Fuchs; Shuji Ogino Journal: Clin Cancer Res Date: 2012-02-22 Impact factor: 12.531