ArticleCancer science2004
Promoter hypermethylation of DAP-kinase is associated with poor survival in primary biliary tract carcinoma patients.
Article in Cancer science, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 67 citations in OpenAlex.
- Emerging omics diagnosis of perihilar cholangiocarcinoma.Journal of gastroenterology · 2026Article
- Cholangiocarcinoma and liver transplantation: What we know so far?World journal of gastrointestinal pathophysiology · 2021Review
- Detecting cholangiocarcinoma in patients with primary sclerosing cholangitis - The promise of DNA methylation and molecular biomarkers.JHEP reports : innovation in hepatology · 2020Review
- Epigenetic biomarkers in gastrointestinal cancers: The current state and clinical perspectives.Seminars in cancer biology · 2018Review
- Gallbladder cancer epidemiology, pathogenesis and molecular genetics: Recent update.World journal of gastroenterology · 2017Review
- Signaling pathways as therapeutic targets in biliary tract cancer.Expert opinion on therapeutic targets · 2017Review
- Epithelial-to-mesenchymal transition in gallbladder cancer: from clinical evidence to cellular regulatory networks.Cell death discovery · 2017Review
- Serum metabolome profiles characterized by patients with hepatocellular carcinoma associated with hepatitis B and C.World journal of gastroenterology · 2016Article
- Global and gene-specific DNA methylation pattern discriminates cholecystitis from gallbladder cancer patients in Chile.Future oncology (London, England) · 2015Article
- Emerging evidence for CHFR as a cancer biomarker: from tumor biology to precision medicine.Cancer metastasis reviews · 2014Review
- The significance of genetics for cholangiocarcinoma development.Annals of translational medicine · 2013Review
- Prognostic significance of epigenetic inactivation of p16, p15, MGMT and DAPK genes in follicular lymphoma.Medical oncology (Northwood, London, England) · 2013Article
- DNA promoter methylation as a diagnostic and therapeutic biomarker in gallbladder cancer.Clinical epigenetics · 2012Article
- Runx3 is required for the differentiation of lung epithelial cells and suppression of lung cancer.Oncogene · 2010Article
- CHFR: A Novel Mitotic Checkpoint Protein and Regulator of Tumorigenesis.Translational oncology · 2008Article
- Suppressing effects of down-regulating DNMT1 and DNMT3b expression on the growth of human cholangiocarcinoma cell line.Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban · 2008Article
- Molecular biomarkers in urothelial bladder cancer.Cancer science · 2008Review
- Epigenetic DNA hypermethylation in cholangiocarcinoma: potential roles in pathogenesis, diagnosis and identification of treatment targets.Liver international : official journal of the International Association for the Study of the Liver · 2008Review
- Two distinct pathways of p16 gene inactivation in gallbladder cancer.World journal of gastroenterology · 2007Article
- Early involvement of death-associated protein kinase promoter hypermethylation in the carcinogenesis of Barrett's esophageal adenocarcinoma and its association with clinical progression.Neoplasia (New York, N.Y.) · 2007Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To clarify the clinicopathological significance of promoter hypermethylation of tumor suppressor and tumor-related genes in biliary tract carcinomas, we examined the promoter methylation status of multiple genes in primary biliary tract carcinomas. These consisted of carcinomas of the bile duct, gallbladder, and duodenal ampulla. Surgical specimens were obtained from a total of 37 patients with biliary tract carcinoma. The cohort consisted of 23 patients with bile duct carcinoma, 9 patients with gallbladder carcinoma, and 5 patients with ampullary carcinoma. The methylation status of CHFR, DAP-kinase, E-cadherin, hMLH1, p16, RASSF1A, and RUNX3 was examined by methylation-specific polymerase chain reaction (MSP). The correlation between methylation status and clinicopathological characteristics was then assessed. The methylation frequencies of CHFR, DAP-kinase, E-cadherin, hMLH1, p16, RASSF1A, and RUNX3 genes were 16.2%, 21.4%, 27.0%, 8.1%, 24.3%, 27.0%, and 56.8%, respectively, in primary biliary tract carcinomas. The number of methylated genes per sample was 2.17 +/- 0.28 (average +/- SD) in bile duct carcinomas, 1.80 +/- 0.97 in ampullary carcinomas, and 0.89 +/- 0.35 in gallbladder carcinomas, with a statistically significant difference between bile duct carcinomas and gallbladder carcinomas (P = 0.02). As for clinicopathological significance, patients with a methylated RUNX3 promoter were significantly older than those with unmethylated RUNX3 (P = 0.01), and DAP-kinase methylation was more frequent in poorly differentiated tumors than in well to moderately differentiated ones (P = 0.04). The overall survival rate was significantly lower in patients with methylated DAP-kinase (P = 0.009) or RUNX3 (P = 0.034) compared to those with unmethylated genes. Furthermore, DAP-kinase methylation-positive status was independently associated with poor survival in multivariate analyses (hazard ratio = 8.71, P = 0.024). A significant proportion of primary biliary tract carcinomas exhibited promoter hypermethylation of tumor suppressor and tumor-related genes, although bile duct carcinomas are more prone to being affected by promoter methylation than are gallbladder carcinomas. Hypermethylation of DAP-kinase appears to be a significant prognostic factor in primary biliary tract carcinomas.
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