Aberrant methylation of MUC1 and MUC4 promoters are potential prognostic biomarkers for pancreatic ductal adenocarcinomas.
Aberrant methylation of MUC1 and MUC4 promoters are potential prognostic biomarkers for pancreatic ductal adenocarcinomas.
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DOI：
10.18632/oncotarget.9924
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发表时间：
2016-07-05
期刊：
影响因子：
--
通讯作者：
Hollingsworth MA
中科院分区：
文献类型：
--
作者：
Yokoyama S;Higashi M;Kitamoto S;Oeldorf M;Knippschild U;Kornmann M;Maemura K;Kurahara H;Wiest E;Hamada T;Kitazono I;Goto Y;Tasaki T;Hiraki T;Hatanaka K;Mataki Y;Taguchi H;Hashimoto S;Batra SK;Tanimoto A;Yonezawa S;Hollingsworth MA
尽管有诊断技术，胰腺癌仍然是一种高死亡率的疾病。黏液蛋白（Mucins， MUC）在胰腺肿瘤的癌变和侵袭中起着至关重要的作用。MUC1和MUC4是高分子量的跨膜粘蛋白。这些分子在许多癌症中过表达，高表达是与预后不良相关的危险因素。我们采用甲基化特异性电泳（MSE）方法对169例不同胰腺病变患者胰腺组织样本中MUC1和MUC4启动子区域的甲基化状态进行了评估。这些结果比较了MUC1和MUC4，几种DNA甲基化/去甲基化因子（如10 - 11易位或TET，激活诱导胞苷脱氨酶或AID）和CAIX（碳酸酐酶IX，作为缺氧生物标志物）的表达。这些结果也与临床病理特征进行了分析，包括PDAC患者的总生存时间。我们发现胰腺组织中MUC1和MUC4启动子的DNA甲基化状态与MUC1和MUC4 mRNA的表达相关。此外，一些DNA甲基化/去甲基化因子的表达与MUC1和MUC4甲基化状态有显著相关性。此外，CAIX的表达与MUC1和MUC4的表达显著相关。有趣的是，我们的研究结果表明MUC1和/或MUC4启动子的低甲基化与总生存率降低相关。这是首次报道MUC1和/或MUC4甲基化状态与预后之间的关系。黏液蛋白基因的表观遗传变化分析可能是诊断PDAC患者的实用工具和预后预测因素之一。
Pancreatic cancer is still a disease of high mortality despite availability of diagnostic techniques. Mucins (MUC) play crucial roles in carcinogenesis and tumor invasion in pancreatic neoplasms. MUC1 and MUC4 are high molecular weight transmembrane mucins. These are overexpressed in many carcinomas, and high expression of these molecules is a risk factor associated with poor prognosis. We evaluated the methylation status of MUC1 and MUC4 promoter regions in pancreatic tissue samples from 169 patients with various pancreatic lesions by the methylation specific electrophoresis (MSE) method. These results were compared with expression of MUC1 and MUC4, several DNA methylation/demethylation factors (e.g. ten-eleven translocation or TET, and activation-induced cytidine deaminase or AID) and CAIX (carbonic anhydrase IX, as a hypoxia biomarker). These results were also analyzed with clinicopathological features including time of overall survival of PDAC patients. We show that the DNA methylation status of the promoters of MUC1 and MUC4 in pancreatic tissue correlates with the expression of MUC1 and MUC4 mRNA. In addition, the expression of several DNA methylation/demethylation factors show a significant correlation with MUC1 and MUC4 methylation status. Furthermore, CAIX expression significantly correlates with the expression of MUC1 and MUC4. Interestingly, our results indicate that low methylation of MUC1 and/or MUC4 promoters correlates with decreased overall survival. This is the first report to show a relationship between MUC1 and/or MUC4 methylation status and prognosis. Analysis of epigenetic changes in mucin genes may be of diagnostic utility and one of the prognostic predictors for patients with PDAC.
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影响因子：
3.8
作者：
Yokoyama S;Kitamoto S;Yamada N;Houjou I;Sugai T;Nakamura S;Arisaka Y;Takaori K;Higashi M;Yonezawa S
通讯作者：
Yonezawa S
影响因子：
11.2
作者：
Singh, AP;Moniaux, N;Batra, SK
通讯作者：
Batra, SK
影响因子：
78.5
作者：
Kufe, Donald W.
通讯作者：
Kufe, Donald W.
影响因子：
8.8
作者：
Mariani CJ;Vasanthakumar A;Madzo J;Yesilkanal A;Bhagat T;Yu Y;Bhattacharyya S;Wenger RH;Cohn SL;Nanduri J;Verma A;Prabhakar NR;Godley LA
通讯作者：
Godley LA
DOI：
10.1126/science.1170116
发表时间：
2009-05-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Tahiliani M;Koh KP;Shen Y;Pastor WA;Bandukwala H;Brudno Y;Agarwal S;Iyer LM;Liu DR;Aravind L;Rao A
通讯作者：
Rao A