The online version of this article (doi:10.1186/1477-7819-10-5) contains supplementary material, which is available to authorized users.
No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.
LXF proposed the study and wrote the first draft of the manuscript. TK analyzed the data. All authors contributed to the design and interpretation of the study and to further drafts. LXF is the guarantor. All authors read and approved the final manuscript'
To study the methylation status of genes that play a role in the p53-Bax mitochondrial apoptosis pathway and its clinical significance in cholangiocarcinoma.
Out of 36 cases cholangiocarcinoma patients from April 2000 to May 2005 were collected.Promoter hypermethylation of DAPK, p14 ARF , and ASC were detected by methylation-specific PCR on cholangiocarcinoma and normal adjacent tissues samples. Mutation of the p53 gene was examined by automated sequencing. Correlation between methylation of these genes and/or p53 mutation status with clinical characteristics of patients was investigated by statistical analysis.
We found 66.7% of 36 cholangiocarcinoma patients had methylation of at least one of the tumor suppressor genes analyzed. p53 gene mutation was found in 22 of 36 patients (61.1%). Combined p53 mutation and DAPK, p14 ARF , and/or ASC methylation was detected in 14 cases (38.9%). There were statistically significant differences in the extent of pathologic biology, differentiation, and invasion between patients with combined p53 mutation and DAPK, p14 ARF , and/or ASC methylation compared to those without (P < 0.05). The survival rate of patients with combined DAPK, p14 ARF , and ASC methylation and p53 mutation was poorer than other patients (P < 0.05).
Our study indicates that methylation of DAPK, p14 ARF , and ASC in cholangiocarcinoma is a common event. Furthermore, p53 mutation combined with DAPK, p14 ARF , and/or ASC methylation correlates with malignancy and poor prognosis.
Authors’ original file for figure 112957_2011_937_MOESM1_ESM.doc
Authors’ original file for figure 212957_2011_937_MOESM2_ESM.pdf
Authors’ original file for figure 312957_2011_937_MOESM3_ESM.pdf
Authors’ original file for figure 412957_2011_937_MOESM4_ESM.pdf
Authors’ original file for figure 512957_2011_937_MOESM5_ESM.doc
Authors’ original file for figure 612957_2011_937_MOESM6_ESM.pdf
Liu XF, Zhu SG, Zhang H: The methylation status of the TMS1/ASC gene in cholangiocarcinoma and its clinical significance. HBPT INT. 2006, 449-453. 5
Liu XF, Zhang H, Zhu SG: Corrlation of p53 gene mutation and expression in cholangiocarcinoma. World J Gastroenterology. 2006, 4609-4772. 12
Paik WH, Park YS, Hwang JH, Lee SH, Yoon CJ, Kang SG: Palliative treatment with self-expandable metallic stents in patients with advanced type III or IV hilar cholangiocarcinoma: a percutaneous versus endoscopic approach. Gastrointest Endosc. 2009, 69: 55-62. 10.1016/j.gie.2008.04.005. CrossRefPubMed
Welzel TM, Graubard BI, El-Serag HB, Shaib YH, Hsing AW, Davila JA, McGlynn KA: Risk factors for intrahepatic and extrahepatic cholangiocarcinoma in the United States: a population-based case-control study. Clin Gastroenterol Hepatol. 2007, 5: 1221-1228. 10.1016/j.cgh.2007.05.020. PubMedCentralCrossRefPubMed
Shaib Y, El-serav HB: The epidemiology of cholangiocarcinoma. Sem in Liver Dis. 2004, 24: 115-125. 10.1055/s-2004-828889. CrossRef
Fraga MF, Uriol E, Diego LB: High performance capillary electrophoretic method for the quantification of 5-methyl-2'-deoxycytidine in genomic DNA:application to plant, animal and human cancer tissues. Electrophoresis. 2002, 1677-1681. 23
Baylin SB, Esteller M, Rountree MR: Aberrant patterns of DNA methylation, chromation and gene expression in cancer. Hum Mol Genet. 2001, 687-692. 10
Ohtsuka T, Liu XF, Koga Y: Methylation-induced silencing of ASC and the effect of expressed ASC on p53-mediated chemosensitivity in colorectal cancer. Oncogene. 2006, 1807-1811. 25
Yuasa Y: DNA methylation in cancer and aging. Mechanisms of aging and development. 2002, 123: 1649-1654. 10.1016/S0047-6374(02)00100-8. CrossRef
- Correlation between promoter methylation of p14 ARF , TMS1/ASC, and DAPK, and p53 mutation with prognosis in cholangiocarcinoma
- BioMed Central
Neu im Fachgebiet Chirurgie
Mail Icon II