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CpG Island Methylator Phenotype and Methylation of Wnt Pathway Genes Together Predict Survival in Patients with Colorectal Cancer

Authors
 Se Hyun Kim  ;  Kyu Hyun Park  ;  Sang Joon Shin  ;  Kang Young Lee  ;  Tae Il Kim  ;  Nam Kyu Kim  ;  Sun Young Rha  ;  Joong Bae Ahn 
Citation
 Yonsei Medical Journal, Vol.59(5) : 588-594, 2018 
Journal Title
 Yonsei Medical Journal 
ISSN
 0513-5796 
Issue Date
2018
Keywords
Colorectal carcinoma ; CpG island methylator phenotype ; DNA methylation ; Wnt pathway
Abstract
PURPOSE: Dysregulation of the Wnt pathway is a crucial step in the tumorigenesis of colorectal cancer (CRC). This study aimed to determine whether DNA methylation of Wnt pathway genes helps predict treatment response and survival in patients with metastatic or recurrent CRC. MATERIALS AND METHODS: We retrospectively collected primary tumor tissues from 194 patients with metastatic or recurrent CRC. Pyrosequencing was used to examine the methylation of 10 CpG island loci in DNA extracted from formalin-fixed paraffin-embedded specimens. To elucidate the predictive role of DNA methylation markers, Kaplan-Meier survival estimation and Cox regression were performed for progression-free survival and overall survival (OS). RESULTS: The methylation frequencies of the 10 genes analyzed (p16, p14, MINT1, MINT2, MINT31, hMLH1, DKK3, WNT5A, AXIN2, and TFAP2E) were 47.9%, 10.8%, 21.1%, 16.0%, 20.6%, 0.5%, 53.1%, 32.0%, 2.6%, and 2.1%, respectively. We divided patients into three groups based on the number of methylated genes (group 1, no methylation n=38; group 2, 1-2 methylations n=92; group 3, 3 or more methylations n=64). Among patients treated with palliative chemotherapy (n=167), median OSs of groups 1, 2, and 3 were 39.1, 39.7, and 29.1 months, respectively (log rank p=0.013). After adjustment, number of methylations was identified as an independent poor prognostic factor (0-2 methylated vs. ≥3 methylated: hazard ratio, 1.72; 95% confidence interval, 1.16-2.56, p=0.007). CONCLUSION: This study suggests that methylation of Wnt pathway genes, in addition to known CpG island methylator phenotype markers, may help predict treatment outcome and survival in patients with CRC.
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DOI
10.3349/ymj.2018.59.5.588
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
김남규(Kim, Nam Kyu) ORCID logo https://orcid.org/0000-0003-0639-5632
김태일(Kim, Tae Il) ORCID logo https://orcid.org/0000-0003-4807-890X
라선영(Rha, Sun Young) ORCID logo https://orcid.org/0000-0002-2512-4531
박규현(Park, Kyu Hyun)
신상준(Shin, Sang Joon) ORCID logo https://orcid.org/0000-0001-5350-7241
안중배(Ahn, Joong Bae) ORCID logo https://orcid.org/0000-0001-6787-1503
이강영(Lee, Kang Young)
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/165518
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