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MAL基因高甲基化是一种组织特异性事件,与食管癌中MAL信使核糖核酸(mRNA)表达相关。

MAL hypermethylation is a tissue-specific event that correlates with MAL mRNA expression in esophageal carcinoma.

作者信息

Jin Zhe, Wang Liang, Zhang Yuan, Cheng Yulan, Gao Yan, Feng Xianling, Dong Ming, Cao Ziyi, Chen Si, Yu Huimin, Zhao Zhenfu, Zhang Xiaojing, Liu Jie, Mori Yuriko, Fan Xinmin, Meltzer Stephen J

机构信息

1] Department of Pathology, The Shenzhen University School of Medicine, Shenzhen, Guangdong, People's Republic of China [2] Shenzhen Key Laboratory of Micromolecule Innovatal Drugs, Shenzhen, Guangdong, People's Republic of China [3] Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, Guangdong, People's Republic of China [4].

出版信息

Sci Rep. 2013 Oct 3;3:2838. doi: 10.1038/srep02838.

Abstract

MAL promoter hypermethylation was examined in 260 human esophageal specimens using real-time quantitative methylation-specific PCR (qMSP). MAL hypermethylation showed highly discriminative ROC curve profiles which clearly distinguished esophageal adenocarcinomas (EAC) from both esophageal squamous cell carcinomas (ESCC) and normal esophagus (NE). Both MAL methylation frequency and normalized methylation value (NMV) were significantly higher in Barrett's esophagus (BE), dysplastic BE, and EAC than in ESCC or in NE. Among matched NE and EAC samples, MAL NMVs in EAC were significantly higher than in corresponding NE. There was a significant correlation between MAL hypermethylation and BE segment length. Treatment with 5-aza-2'-deoxycytidine reversed MAL methylation and reactivated MAL mRNA expression in OE33 EAC cells. MAL mRNA levels in EACs with unmethylated MAL were significantly higher than in EACs with methylated MAL. MAL hypermethylation is a common, tissue-specific event in human EAC and correlates with clinical neoplastic progression risk factors.

摘要

使用实时定量甲基化特异性PCR(qMSP)检测了260例人食管标本中的MAL启动子高甲基化情况。MAL高甲基化表现出高度有鉴别力的ROC曲线特征,能清晰地区分食管腺癌(EAC)与食管鳞状细胞癌(ESCC)以及正常食管(NE)。Barrett食管(BE)、发育异常的BE和EAC中的MAL甲基化频率和标准化甲基化值(NMV)均显著高于ESCC或NE。在配对的NE和EAC样本中,EAC中的MAL NMV显著高于相应的NE。MAL高甲基化与BE段长度之间存在显著相关性。用5-氮杂-2'-脱氧胞苷处理可逆转OE33 EAC细胞中的MAL甲基化并重新激活MAL mRNA表达。MAL未甲基化的EAC中的MAL mRNA水平显著高于MAL甲基化的EAC。MAL高甲基化是人类EAC中常见的组织特异性事件,并且与临床肿瘤进展风险因素相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bef/3789153/31a6befbb5b6/srep02838-f1.jpg

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