Tags

Type your tag names separated by a space and hit enter

Promoter methylation of the Wnt/beta-catenin signaling antagonist Dkk-3 is associated with poor survival in gastric cancer.
Cancer. 2009 Jan 01; 115(1):49-60.C

Abstract

BACKGROUND

Abnormal activation of the Wnt/beta-catenin signaling pathway is common and critical in the pathogenesis of digestive cancers. In this study, the authors investigated the promoter methylation of the dickkopf homolog 3 gene Dkk-3 in these cancers and its prognostic significance in gastric cancer.

METHODS

Dkk-3 methylation was assessed in 173 patients with gastric cancers (including 104 patients who were followed for up to 4090 days) and in 128 patients with colorectal cancer. Cell growth was evaluated by using a colony-formation assay. For survival analyses, the authors used Kaplan-Meier plots, the log-rank test, and Cox proportional regression.

RESULTS

Dkk-3 was silenced or down-regulated in 12 of 17 gastric cancer cell lines (70.6%) and in 3 of 9 colon cancer cell lines (33.3%). The loss of gene expression was associated with promoter methylation, which could be restored by demethylating agents. Ectopic expression of Dkk-3 suppressed colony formation. Moreover, methylation of Dkk-3 was detected in 117 of 173 primary gastric tumors (67.6%) and in 67 of 128 colorectal tumors (52.3%). The clinical significance and the prognostic value of Dkk-3 methylation also were examined in 104 gastric cancers and in 84 colorectal cancers. Multivariate analysis indicated that Dkk-3 methylation was associated significantly and independently with poor disease survival (relative risk, 2.534; 95% confidence interval, 1.54-4.17; P=.002) in gastric cancer, but not in colorectal cancer. Kaplan-Meier survival curves revealed that patients who had Dkk-3 methylated gastric cancers had a significantly shorter survival (median, 0.76 years) compared with patients who did not have Dkk-3 methylation (median, 2.68 years; P<.0001; log-rank test).

CONCLUSIONS

Epigenetic silencing of the Dkk-3 gene by promoter methylation was a common event in gastric cancer and was associated with a poor outcome in such patients.

Authors+Show Affiliations

Institute of Digestive Disease, Department of Medicine, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong SAR. junyu@cuhk.edu.hkNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19051296

Citation

Yu, Jun, et al. "Promoter Methylation of the Wnt/beta-catenin Signaling Antagonist Dkk-3 Is Associated With Poor Survival in Gastric Cancer." Cancer, vol. 115, no. 1, 2009, pp. 49-60.
Yu J, Tao Q, Cheng YY, et al. Promoter methylation of the Wnt/beta-catenin signaling antagonist Dkk-3 is associated with poor survival in gastric cancer. Cancer. 2009;115(1):49-60.
Yu, J., Tao, Q., Cheng, Y. Y., Lee, K. Y., Ng, S. S., Cheung, K. F., Tian, L., Rha, S. Y., Neumann, U., Röcken, C., Ebert, M. P., Chan, F. K., & Sung, J. J. (2009). Promoter methylation of the Wnt/beta-catenin signaling antagonist Dkk-3 is associated with poor survival in gastric cancer. Cancer, 115(1), 49-60. https://doi.org/10.1002/cncr.23989
Yu J, et al. Promoter Methylation of the Wnt/beta-catenin Signaling Antagonist Dkk-3 Is Associated With Poor Survival in Gastric Cancer. Cancer. 2009 Jan 1;115(1):49-60. PubMed PMID: 19051296.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Promoter methylation of the Wnt/beta-catenin signaling antagonist Dkk-3 is associated with poor survival in gastric cancer. AU - Yu,Jun, AU - Tao,Qian, AU - Cheng,Yuen Y, AU - Lee,Kwan Y, AU - Ng,Simon S M, AU - Cheung,Kin F, AU - Tian,Linwei, AU - Rha,Sun Y, AU - Neumann,Ulf, AU - Röcken,Christoph, AU - Ebert,Matthias P A, AU - Chan,Francis K L, AU - Sung,Joseph J Y, PY - 2008/12/4/pubmed PY - 2009/3/11/medline PY - 2008/12/4/entrez SP - 49 EP - 60 JF - Cancer JO - Cancer VL - 115 IS - 1 N2 - BACKGROUND: Abnormal activation of the Wnt/beta-catenin signaling pathway is common and critical in the pathogenesis of digestive cancers. In this study, the authors investigated the promoter methylation of the dickkopf homolog 3 gene Dkk-3 in these cancers and its prognostic significance in gastric cancer. METHODS: Dkk-3 methylation was assessed in 173 patients with gastric cancers (including 104 patients who were followed for up to 4090 days) and in 128 patients with colorectal cancer. Cell growth was evaluated by using a colony-formation assay. For survival analyses, the authors used Kaplan-Meier plots, the log-rank test, and Cox proportional regression. RESULTS: Dkk-3 was silenced or down-regulated in 12 of 17 gastric cancer cell lines (70.6%) and in 3 of 9 colon cancer cell lines (33.3%). The loss of gene expression was associated with promoter methylation, which could be restored by demethylating agents. Ectopic expression of Dkk-3 suppressed colony formation. Moreover, methylation of Dkk-3 was detected in 117 of 173 primary gastric tumors (67.6%) and in 67 of 128 colorectal tumors (52.3%). The clinical significance and the prognostic value of Dkk-3 methylation also were examined in 104 gastric cancers and in 84 colorectal cancers. Multivariate analysis indicated that Dkk-3 methylation was associated significantly and independently with poor disease survival (relative risk, 2.534; 95% confidence interval, 1.54-4.17; P=.002) in gastric cancer, but not in colorectal cancer. Kaplan-Meier survival curves revealed that patients who had Dkk-3 methylated gastric cancers had a significantly shorter survival (median, 0.76 years) compared with patients who did not have Dkk-3 methylation (median, 2.68 years; P<.0001; log-rank test). CONCLUSIONS: Epigenetic silencing of the Dkk-3 gene by promoter methylation was a common event in gastric cancer and was associated with a poor outcome in such patients. SN - 0008-543X UR - https://www.unboundmedicine.com/medline/citation/19051296/Promoter_methylation_of_the_Wnt/beta_catenin_signaling_antagonist_Dkk_3_is_associated_with_poor_survival_in_gastric_cancer_ L2 - https://doi.org/10.1002/cncr.23989 DB - PRIME DP - Unbound Medicine ER -