Increased frequency of CpG island methylator phenotype and CDH1 methylation in a gastric cancer high-risk region of china.
Increased frequency of CpG island methylator phenotype and CDH1 methylation in a gastric cancer high-risk region of china.
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DOI：
10.1593/tlo.07103
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发表时间：
2008-03
影响因子：
5
通讯作者：
Kai‐Li Zhang;Yuan Sun;Yan Li;Ming Liu;Bo Qu;Shu-Hong Cui;Qing-you Kong;Xiao-yan Chen;Hong Li;Jia Liu
中科院分区：
文献类型：
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作者：
Kai‐Li Zhang;Yuan Sun;Yan Li;Ming Liu;Bo Qu;Shu-Hong Cui;Qing-you Kong;Xiao-yan Chen;Hong Li;Jia Liu
本研究旨在分析47名大连长期居民胃癌患者和31名非胃癌患者胃标本中CDH1/E-cadherin和5个CpG岛甲基化表型（CIMP）相关基因（p16、hMLH1、MINT1、MINT2和MINT31）的甲基化状态。CIMP模式分为三个以上甲基化基因的CIMP- h，一个到两个甲基化基因的CIMP- l和没有甲基化的CIMP- n。47例胃癌中，24例（51.1%）为CIMP-H， 18例（38.3%）为CIMP-L， 5例（10.6%）为CIMP-N，而21例癌前病变中5例（23.8%）为CIMP-H， 15例（71.4%）为CIMP-L。CIMP-L存在于75%（12/16）的气相色谱邻近粘膜中，38.7%（12/31）的无气相色谱患者粘膜中。48.9%（23/47）的肿瘤、23.8%（5/21）的癌前组织和25%（4/16）的非癌组织发生了CDH1甲基化，并与患者年龄（P = 0.01）、淋巴结转移和CIMP严重程度（P = 0.000 - 0.028）相关。我们的研究结果表明，CIMP-H在大连GC中的频率，CIMP-L和p16在GC邻近组织和无GC粘膜中的甲基化频率远高于之前报道的频率，表明该GC高风险区域的甲基化压力升高。CDH1甲基化与CIMP严重程度密切相关，提示在GC预防和早期诊断中有必要联合用药。
This study aimed to profile the methylation statuses of CDH1/E-cadherin and five CpG island methylator phenotype (CIMP)-associated genes (p16, hMLH1, MINT1, MINT2, and MINT31) in gastric specimens of 47 Dalian long-term residents with and 31 without gastric cancers (GCs). CIMP patterns were classified as CIMP-H with over three methylated genes, CIMP-L with one to two methylated genes, and CIMP-N without methylation. Of 47 GC cases, 24 (51.1%) were CIMP-H, 18 (38.3%) were CIMP-L, and 5 (10.6%) were CIMP-N, whereas 5 of 21 (23.8%) premalignant lesions were CIMP-H and 15 (71.4%) were CIMP-L. CIMP-L was found in 75% (12/16) of GC-adjacent mucosa and in 38.7% (12/31) of mucosa from GC-free patients. CDH1 methylation occurred in 48.9% (23/47) of cancer, in 23.8% (5/21) of premalignant, and in 25% (4/16) of noncancerous tissues and was correlated with patients' age (P = .01), lymph node metastasis, and CIMP severity (P = .000-.028). Our results demonstrated that the frequencies of CIMP-H in Dalian GCs, CIMP-L, and p16 methylation in GC-adjacent tissues and in GC-free mucosa were much higher than those reported previously, indicating the elevated methylation pressure in this GC high-risk region. The close correlation between CDH1 methylation and CIMP severity suggests the necessity of their combination in GC prevention and earlier diagnosis.