Clinico-epigenetic combination including quantitative methylation value of DKK3 augments survival prediction of the patient with cervical cancer

Woong Sun Kang, Sung Bum Cho, Junsoo Park, Moo Yul Lee, Soon Chul Myung, Won Yong Kim, Sang Hoon Lee, Dong Ho Kim, Eun Ju Lee

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Purpose: DKK3 is a target of methylation in various cancers and has been studied by a non-quantitative method. We assessed the quantitative methylation levels of DKK3 in cervical carcinoma, determined the potential clinical correlations, and tested whether the combination of clinical and epigenetic factors augmented the prediction power of prognosis. Methods: Sixty-two patients with cervical squamous cell carcinoma were included in this study. Quantitative methylation levels were evaluated by pyrosequencing. Clinical and pathologic findings were obtained from medical records. Survival data were analyzed using Kaplan-Meier estimates and compared with the log-rank test. The best clinico-epigenetic combinations were found using the Cox proportional hazard model. Results: Four of five CpG positions of DKK3 were strongly methylated in cervical carcinoma compared to normal controls (p = 0.0048). The methylation in positions 1 and/or 2 were stronger in patients with higher serum levels of the SCC tumor marker and/or larger tumors (p = 0.01). The patients with a methylation level ≥26.3 % at position 1 had a lower survival rate than the patients with methylation levels at position 1 that were <26.3 % (p = 0.03). The combination of methylation level of position 1, position 3, age, parametrial invasion, and lymphovascular space invasion (LVSI) have a significant correlation with survival (p = 0.0006). Recurrence was significantly related to the combination of methylation level of position 2, position 3, age, parametrium, and LVSI (p = 0.0041). Conclusions: DKK3 methylation is unfavorable to prognosis. This study defined a threshold level of methylation associated with recurrence-free survival and, furthermore, identified novel clinico-epigenetic combinations predicting disease survival or recurrence.

Original languageEnglish
Pages (from-to)97-106
Number of pages10
JournalJournal of cancer research and clinical oncology
Volume139
Issue number1
DOIs
Publication statusPublished - 2013 Jan 1

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Epigenomics
Uterine Cervical Neoplasms
Methylation
Survival
Recurrence
Carcinoma
Peritoneum
Kaplan-Meier Estimate
Tumor Biomarkers
Proportional Hazards Models
Medical Records
Squamous Cell Carcinoma
Neoplasms
Survival Rate
Serum

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Kang, Woong Sun ; Cho, Sung Bum ; Park, Junsoo ; Lee, Moo Yul ; Myung, Soon Chul ; Kim, Won Yong ; Lee, Sang Hoon ; Kim, Dong Ho ; Lee, Eun Ju. / Clinico-epigenetic combination including quantitative methylation value of DKK3 augments survival prediction of the patient with cervical cancer. In: Journal of cancer research and clinical oncology. 2013 ; Vol. 139, No. 1. pp. 97-106.
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abstract = "Purpose: DKK3 is a target of methylation in various cancers and has been studied by a non-quantitative method. We assessed the quantitative methylation levels of DKK3 in cervical carcinoma, determined the potential clinical correlations, and tested whether the combination of clinical and epigenetic factors augmented the prediction power of prognosis. Methods: Sixty-two patients with cervical squamous cell carcinoma were included in this study. Quantitative methylation levels were evaluated by pyrosequencing. Clinical and pathologic findings were obtained from medical records. Survival data were analyzed using Kaplan-Meier estimates and compared with the log-rank test. The best clinico-epigenetic combinations were found using the Cox proportional hazard model. Results: Four of five CpG positions of DKK3 were strongly methylated in cervical carcinoma compared to normal controls (p = 0.0048). The methylation in positions 1 and/or 2 were stronger in patients with higher serum levels of the SCC tumor marker and/or larger tumors (p = 0.01). The patients with a methylation level ≥26.3 {\%} at position 1 had a lower survival rate than the patients with methylation levels at position 1 that were <26.3 {\%} (p = 0.03). The combination of methylation level of position 1, position 3, age, parametrial invasion, and lymphovascular space invasion (LVSI) have a significant correlation with survival (p = 0.0006). Recurrence was significantly related to the combination of methylation level of position 2, position 3, age, parametrium, and LVSI (p = 0.0041). Conclusions: DKK3 methylation is unfavorable to prognosis. This study defined a threshold level of methylation associated with recurrence-free survival and, furthermore, identified novel clinico-epigenetic combinations predicting disease survival or recurrence.",
author = "Kang, {Woong Sun} and Cho, {Sung Bum} and Junsoo Park and Lee, {Moo Yul} and Myung, {Soon Chul} and Kim, {Won Yong} and Lee, {Sang Hoon} and Kim, {Dong Ho} and Lee, {Eun Ju}",
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Clinico-epigenetic combination including quantitative methylation value of DKK3 augments survival prediction of the patient with cervical cancer. / Kang, Woong Sun; Cho, Sung Bum; Park, Junsoo; Lee, Moo Yul; Myung, Soon Chul; Kim, Won Yong; Lee, Sang Hoon; Kim, Dong Ho; Lee, Eun Ju.

In: Journal of cancer research and clinical oncology, Vol. 139, No. 1, 01.01.2013, p. 97-106.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Clinico-epigenetic combination including quantitative methylation value of DKK3 augments survival prediction of the patient with cervical cancer

AU - Kang, Woong Sun

AU - Cho, Sung Bum

AU - Park, Junsoo

AU - Lee, Moo Yul

AU - Myung, Soon Chul

AU - Kim, Won Yong

AU - Lee, Sang Hoon

AU - Kim, Dong Ho

AU - Lee, Eun Ju

PY - 2013/1/1

Y1 - 2013/1/1

N2 - Purpose: DKK3 is a target of methylation in various cancers and has been studied by a non-quantitative method. We assessed the quantitative methylation levels of DKK3 in cervical carcinoma, determined the potential clinical correlations, and tested whether the combination of clinical and epigenetic factors augmented the prediction power of prognosis. Methods: Sixty-two patients with cervical squamous cell carcinoma were included in this study. Quantitative methylation levels were evaluated by pyrosequencing. Clinical and pathologic findings were obtained from medical records. Survival data were analyzed using Kaplan-Meier estimates and compared with the log-rank test. The best clinico-epigenetic combinations were found using the Cox proportional hazard model. Results: Four of five CpG positions of DKK3 were strongly methylated in cervical carcinoma compared to normal controls (p = 0.0048). The methylation in positions 1 and/or 2 were stronger in patients with higher serum levels of the SCC tumor marker and/or larger tumors (p = 0.01). The patients with a methylation level ≥26.3 % at position 1 had a lower survival rate than the patients with methylation levels at position 1 that were <26.3 % (p = 0.03). The combination of methylation level of position 1, position 3, age, parametrial invasion, and lymphovascular space invasion (LVSI) have a significant correlation with survival (p = 0.0006). Recurrence was significantly related to the combination of methylation level of position 2, position 3, age, parametrium, and LVSI (p = 0.0041). Conclusions: DKK3 methylation is unfavorable to prognosis. This study defined a threshold level of methylation associated with recurrence-free survival and, furthermore, identified novel clinico-epigenetic combinations predicting disease survival or recurrence.

AB - Purpose: DKK3 is a target of methylation in various cancers and has been studied by a non-quantitative method. We assessed the quantitative methylation levels of DKK3 in cervical carcinoma, determined the potential clinical correlations, and tested whether the combination of clinical and epigenetic factors augmented the prediction power of prognosis. Methods: Sixty-two patients with cervical squamous cell carcinoma were included in this study. Quantitative methylation levels were evaluated by pyrosequencing. Clinical and pathologic findings were obtained from medical records. Survival data were analyzed using Kaplan-Meier estimates and compared with the log-rank test. The best clinico-epigenetic combinations were found using the Cox proportional hazard model. Results: Four of five CpG positions of DKK3 were strongly methylated in cervical carcinoma compared to normal controls (p = 0.0048). The methylation in positions 1 and/or 2 were stronger in patients with higher serum levels of the SCC tumor marker and/or larger tumors (p = 0.01). The patients with a methylation level ≥26.3 % at position 1 had a lower survival rate than the patients with methylation levels at position 1 that were <26.3 % (p = 0.03). The combination of methylation level of position 1, position 3, age, parametrial invasion, and lymphovascular space invasion (LVSI) have a significant correlation with survival (p = 0.0006). Recurrence was significantly related to the combination of methylation level of position 2, position 3, age, parametrium, and LVSI (p = 0.0041). Conclusions: DKK3 methylation is unfavorable to prognosis. This study defined a threshold level of methylation associated with recurrence-free survival and, furthermore, identified novel clinico-epigenetic combinations predicting disease survival or recurrence.

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