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, Namkyu Kim, SunYoung Rha, Joong Bae Ahn

Research output: Contribution to journalArticle

3 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 1

Fingerprint

CpG Islands
Wnt Signaling Pathway
Methylation
Colorectal Neoplasms
Phenotype
Survival
Genes
DNA Methylation
p16 Genes
Genetic Markers
Gene Frequency
Paraffin
Formaldehyde
Disease-Free Survival
Carcinogenesis
Confidence Intervals
Drug Therapy
DNA

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Kim, Se Hyun ; Park, Kyu Hyun ; Shin, Sang Joon ; Lee, Kang Young ; Kim, Tae Il ; Kim, Namkyu ; Rha, SunYoung ; Ahn, Joong Bae. / CpG island methylator phenotype and methylation of wnt pathway genes together predict survival in patients with colorectal cancer. In: Yonsei medical journal. 2018 ; Vol. 59, No. 5. pp. 588-594.
@article{158fbfda69d14910aff4b560ca33d05d,
title = "CpG island methylator phenotype and methylation of wnt pathway genes together predict survival in patients with colorectal cancer",
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.",
author = "Kim, {Se Hyun} and Park, {Kyu Hyun} and Shin, {Sang Joon} and Lee, {Kang Young} and Kim, {Tae Il} and Namkyu Kim and SunYoung Rha and Ahn, {Joong Bae}",
year = "2018",
month = "7",
day = "1",
doi = "10.3349/ymj.2018.59.5.588",
language = "English",
volume = "59",
pages = "588--594",
journal = "Yonsei Medical Journal",
issn = "0513-5796",
publisher = "Yonsei University College of Medicine",
number = "5",

}

CpG island methylator phenotype and methylation of wnt pathway genes together predict survival in patients with colorectal cancer. / Kim, Se Hyun; Park, Kyu Hyun; Shin, Sang Joon; Lee, Kang Young; Kim, Tae Il; Kim, Namkyu; Rha, SunYoung; Ahn, Joong Bae.

In: Yonsei medical journal, Vol. 59, No. 5, 01.07.2018, p. 588-594.

Research output: Contribution to journalArticle

TY - JOUR

T1 - CpG island methylator phenotype and methylation of wnt pathway genes together predict survival in patients with colorectal cancer

AU - Kim, Se Hyun

AU - Park, Kyu Hyun

AU - Shin, Sang Joon

AU - Lee, Kang Young

AU - Kim, Tae Il

AU - Kim, Namkyu

AU - Rha, SunYoung

AU - Ahn, Joong Bae

PY - 2018/7/1

Y1 - 2018/7/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85048152387&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85048152387&partnerID=8YFLogxK

U2 - 10.3349/ymj.2018.59.5.588

DO - 10.3349/ymj.2018.59.5.588

M3 - Article

VL - 59

SP - 588

EP - 594

JO - Yonsei Medical Journal

JF - Yonsei Medical Journal

SN - 0513-5796

IS - 5

ER -