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 language | English |
|---|---|
| Pages (from-to) | 588-594 |
| Number of pages | 7 |
| Journal | Yonsei medical journal |
| Volume | 59 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2018 Jul |
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- Medicine(all)
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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, Nam Kyu; Rha, Sun Young; Ahn, Joong Bae.
In: Yonsei medical journal, Vol. 59, No. 5, 07.2018, p. 588-594.Research output: Contribution to journal › Article
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, Nam Kyu
AU - Rha, Sun Young
AU - Ahn, Joong Bae
PY - 2018/7
Y1 - 2018/7
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.
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U2 - 10.3349/ymj.2018.59.5.588
DO - 10.3349/ymj.2018.59.5.588
M3 - Article
C2 - 29869456
AN - SCOPUS:85048152387
VL - 59
SP - 588
EP - 594
JO - Yonsei Medical Journal
JF - Yonsei Medical Journal
SN - 0513-5796
IS - 5
ER -