Abstract
BackgroundTo study the methylation status of genes that play a role in the p53-Bax mitochondrial apoptosis pathway and its clinical significance in cholangiocarcinoma.Patients and MethodsOut of 36 cases cholangiocarcinoma patients from April 2000 to May 2005 were collected.Promoter hypermethylation of DAPK, p14ARF, 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.ResultsWe 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, p14ARF, 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, p14ARF, and/or ASC methylation compared to those without (P < 0.05). The survival rate of patients with combined DAPK, p14ARF, and ASC methylation and p53 mutation was poorer than other patients (P < 0.05).ConclusionOur study indicates that methylation of DAPK, p14ARF, and ASC in cholangiocarcinoma is a common event. Furthermore, p53 mutation combined with DAPK, p14ARF, and/or ASC methylation correlates with malignancy and poor prognosis.
Highlights
To study the methylation status of genes that play a role in the p53-Bax mitochondrial apoptosis pathway and its clinical significance in cholangiocarcinoma
Combined p53 mutation and DAPK, p14ARF, and/or ASC methylation was detected in 14 cases (38.9%)
Our study indicates that methylation of DAPK, p14ARF, and ASC in cholangiocarcinoma is a common event
Summary
To study the methylation status of genes that play a role in the p53-Bax mitochondrial apoptosis pathway and its clinical significance in cholangiocarcinoma. Apoptosis or programmed cell death is a normal physiological control mechanism that is critical in maintaining homeostasis. Apoptotic inhibition can lead to abnormal cell survival and carcinogenesis. The p53-Bax mitochondrial apoptosis pathway plays an important role in inducing cell death after DNA damage or under conditions of cellular stress [1]. Some genes in the pathway have latent methylation sites, such as p14ARF, DAPK, and ASC/TMS1, which can be methylated and inactivated resulting in cancer development [2]. Studies investigating methylation of gene that play a role in activation of the p53-Bax mitochondrial apoptosis pathway has not been
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