The increase in the expression and hypomethylation of MUC4 gene with the progression of pancreatic ductal adenocarcinoma
The increase in the expression and hypomethylation of MUC4 gene with the progression of pancreatic ductal adenocarcinoma
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MUC4基因表达量随胰腺导管腺癌进展而增加及低甲基化
DOI：
10.1007/s12032-010-9683-0
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发表时间：
2011-12
期刊：
影响因子：
3.4
通讯作者：
Miao, Yi
中科院分区：
文献类型：
--
作者：
Zhu, Yi;Zhang, Jing-jing;Zhu, Rong;Zhu, Yan;Liang, Wen-biao;Gao, Wen-tao;Yu, Jun-bo;Xu, Ze-kuan;Miao, Yi
MUC4基因可能在胰腺癌的进展中起关键作用，但其在临床组织样本中表达的定量测量仍然是一个挑战。体内MUC4启动子甲基化状态与胰腺癌进展或MUC4 mRNA表达之间的相关性需要证明。采用实时荧光定量PCR和DNA甲基化特异性PCR结合显微切割技术，对57例胰腺导管腺癌患者116个显微切割灶中MUC4的表达和启动子甲基化状态进行了精确检测。mRNA表达和低甲基化频率从正常到癌前病变到胰腺癌均增加。多因素考克斯回归分析显示MUC4高表达（P= 0.008）和肿瘤淋巴结转移分期（P= 0.038）是预测57例患者预后的独立危险因素。30例胰腺导管腺癌组织中MUC4 mRNA表达与其启动子甲基化状态无明显相关性。这些结果表明，高mRNA表达和低甲基化的MUC4基因可能参与胰腺导管腺癌的发生和恶性发展。MUC4 mRNA表达可能成为胰腺癌新的预后指标。基于显微切割的实时定量PCR和甲基化特异性PCR有助于定量检测临床样本中MUC4的表达，并反映MUC4在体内的表观遗传调控机制。
The MUC4 gene could have a key role in the progression of pancreatic cancer, but the quantitative measurement of its expression in clinical tissue samples remains a challenge. The correlations between MUC4 promoter methylation status in vivo and either pancreatic cancer progression or MUC4 mRNA expression need to be demonstrated. We used the techniques of quantitative real-time PCR and DNA methylation-specific PCR combined microdissection to precisely detect MUC4 expression and promoter methylation status in 116 microdissected foci from 57 patients with pancreatic ductal adenocarcinoma. Both mRNA expression and hypomethylation frequency increased from normal to precancerous lesions to pancreatic cancer. Multivariate Cox regression analysis showed that high-level MUC4 expression (P= 0.008) and tumor-node-metastasis staging (P= 0.038) were significant independent risk factors for predicting the prognosis of 57 patients. The MUC4 mRNA expression was not significantly correlated with promoter methylation status in 30 foci of pancreatic ductal adenocarcinoma. These results suggest that high mRNA expression and hypomethylation of the MUC4 gene could be involved in carcinogenesis and in the malignant development of pancreatic ductal adenocarcinoma. The MUC4 mRNA expression may become a new prognostic marker for pancreatic cancer. Microdissection-based quantitative real-time PCR and methylation-specific PCR contribute to the quantitative detection of MUC4 expression in clinical samples and reflect the epigenetic regulatory mechanisms of MUC4 in vivo.
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DOI：
--
发表时间：
2001-12
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
M. Andrianifahanana;N. Moniaux;B. Schmied;J. Ringel;H. Friess;M. Hollingsworth;M. Büchler;J. Aubert;S. Batra
通讯作者：
M. Andrianifahanana;N. Moniaux;B. Schmied;J. Ringel;H. Friess;M. Hollingsworth;M. Büchler;J. Aubert;S. Batra
影响因子：
11.2
作者：
Singh, AP;Moniaux, N;Batra, SK
通讯作者：
Batra, SK
DOI：
--
发表时间：
1989
期刊：
Critical reviews in diagnostic imaging
影响因子：
--
作者：
J. Hanley
通讯作者：
J. Hanley
影响因子：
8
作者：
Andrianifahanana, M;Agrawal, A;Batra, SK
通讯作者：
Batra, SK
影响因子：
3.4
作者：
Saitou, M;Goto, M;Yonezawa, S
通讯作者：
Yonezawa, S