CpG island methylator phenotype and methylation of wnt pathway genes together predict survival in patients with colorectal cancer

Se Hyun Kim, Kyu Hyun Park, Sang Joon Shin, Kang Young Lee, Tae Il Kim, Nam Kyu Kim, Sun Young Rha, Joong Bae Ahn

Research output: Contribution to journalArticle

9 Citations (Scopus)

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-em-bedded 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.

Original languageEnglish
Pages (from-to)588-594
Number of pages7
JournalYonsei medical journal
Volume59
Issue number5
DOIs
Publication statusPublished - 2018 Jul

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Fingerprint Dive into the research topics of 'CpG island methylator phenotype and methylation of wnt pathway genes together predict survival in patients with colorectal cancer'. Together they form a unique fingerprint.

  • Cite this