Correlation between promoter methylation of p14(ARF), TMS1/ASC, and DAPK, and p53 mutation with prognosis in cholangiocarcinoma.
Correlation between promoter methylation of p14(ARF), TMS1/ASC, and DAPK, and p53 mutation with prognosis in cholangiocarcinoma.
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DOI：
10.1186/1477-7819-10-5
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发表时间：
2012-01-09
影响因子：
3.2
通讯作者：
Hailong S
中科院分区：
文献类型：
--
作者：
Xiaofang L;Kun T;Shaoping Y;Zaiqiu W;Hailong S
目的：研究胆管癌细胞中P53-Bax线粒体凋亡途径相关基因的甲基化状态及其临床意义。收集2000年4月至2005年5月收治的36例胆管细胞癌标本，采用甲基化特异性聚合酶链式反应技术检测胆管细胞癌及癌旁正常组织中DAPK、p14ARF和ASC基因启动子的甲基化状态。用自动测序法检测P53基因突变情况。统计分析这些基因甲基化和/或P53突变状态与患者临床特征的关系。我们发现，在36名胆管癌患者中，有66.7%的患者至少有一个抑癌基因发生了甲基化。P53基因突变率为61.1%(22/36)。14例(38.9%)P53基因突变与DAPK、p14ARF和/或ASC甲基化同时存在。联合检测p53基因突变和DAPK、p14ARF和/或ASC甲基化的患者在病理生物学、分化程度和侵袭性方面与无突变患者相比差异有统计学意义(P<；0.05)。DAPK、p14ARF、ASC甲基化和p53突变联合表达患者的生存率低于其他患者(P<；0.05)。我们的研究表明，DAPK、p14ARF和ASC的甲基化在胆管细胞癌中是常见的事件。此外，P53突变、DAPK、p14ARF和/或ASC甲基化与恶性程度和预后不良相关。
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, 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. 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, 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). Our 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.
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影响因子：
3.5
作者：
Baylin, SB;Esteller, M;Herman, JG
通讯作者：
Herman, JG
影响因子：
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