Promoter methylation and expression of TIMP3 gene in gastric cancer.
Promoter methylation and expression of TIMP3 gene in gastric cancer.
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DOI：
10.1186/1746-1596-8-110
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发表时间：
2013-07-02
影响因子：
2.6
通讯作者：
Dai D
中科院分区：
文献类型：
--
作者：
Guan Z;Zhang J;Song S;Dai D
胃癌的发生是一个多阶段的过程，涉及多个基因。DNA甲基化的异常变化被认为是导致抑癌基因失活的第三种机制，在肿瘤的发生发展中起着至关重要的作用。本研究旨在探讨基质金属蛋白酶组织抑制剂3（TIMP 3）基因启动子区CpG岛甲基化及其蛋白表达与胃腺癌临床病理特征的关系。采用甲基化特异性PCR（MSP）和免疫组化方法检测78例胃腺癌组织及癌旁正常黏膜组织中TIMP 3基因启动子区CpG岛甲基化状态和蛋白表达。TIMP 3基因CpG岛甲基化在肿瘤组织、癌旁组织和转移淋巴结中均有表达。按递增顺序，这些组织的甲基化频率为35.9%（28/78例非肿瘤组织），85%（17/20例早期病例），89.7%（52/58例进展期病例）和100%（78/78例转移淋巴结）。肿瘤组织与非肿瘤组织间差异有显著性（P < 0.05），而肿瘤亚组间差异无显著性（P > 0.05）。免疫组化分析证实TIMP 3在肿瘤组织中表达下调。TIMP 3基因在非肿瘤组织中的表达率为100%，但在不同的阶段，即，在早期癌灶中，阳性率为30%（6/20），进展期癌灶中，阳性率为3.4%（2/58），转移淋巴结癌灶中，阳性率为0%（0/78）。在70例TIMP 3阴性表达的肿瘤组织中，64例（91.4%）甲基化，6例（8.6%）未甲基化，提示TIMP 3表达降低或阴性与肿瘤组织甲基化有显著相关性（P < 0.01）。TIMP 3基因启动子区CpG岛甲基化是TIMP 3基因表达的主要机制，可能为胃癌的分子诊断和分期提供依据。本文的虚拟幻灯片可以在这里找到：http://www.diagnosticpathology.diagnomx.eu/vs/1756134016954958
Gastric carcinoma development is a multi-stage process that involves more than one gene. Aberrant changes in DNA methylation are considered as the third mechanism that leads to anti-oncogene inactivation, which plays an essential role in tumor development. In this study, we assessed the relationship among the aberrant methylation of the promoter CpG islands of tissue inhibitor of metalloproteinase 3 (TIMP3) gene, its protein expression, and the clinicopathological features of gastric adenocarcinoma. The methylation status of the promoter CpG islands and the protein expression of TIMP3 gene in tumors and adjacent normal mucosal tissues of 78 patients with gastric adenocarcinoma were detected by methylation-specific PCR (MSP) and immunohistochemistry. The CpG island methylation of TIMP3 was detected in tumor tissues, cancer-adjacent tissues, and lymph nodes with metastasis. In increasing order, the hypermethylation frequency of these tissues were 35.9% (28 of 78 non-neoplastic tissues), 85% (17 of 20 early-stage cases), 89.7% (52 of 58 progressive-stage cases), and 100% (78 of 78 metastatic lymph node). A marked difference was found between tumors and non-neoplastic tissues (P < 0.05), but no difference existed among the subgroups of tumors (P > 0.05). Immunohistochemistry analysis confirmed TIMP3 down-regulation in tumor tissues. The rate of TIMP3 gene expression was 100% in non-neoplastic tissues but apparently decreased to various extents at different stages, i.e., decreased to 30% (6/20) at the early stage, to 3.4% (2/58) at the progressive stage, and to 0% (0/78) in metastatic lymph nodes. Among the 70 tumor tissues with negative TIMP3 expression, 64 (91.4%) were hypermethylated and 6 were unmethylated (8.6%), indicating a significant association between hypermethylation and reduced or negative TIMP3 expression (P < 0.01). The hypermethylation of the promoter region in CpG islands is the main mechanism of TIMP3 gene expression and may provide evidence for the molecular diagnosis and stage evaluation of gastric cancer. The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1756134016954958
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DOI：
10.1073/pnas.93.18.9821
发表时间：
1996-09-03
影响因子：
11.1
作者：
Herman, JG;Graff, JR;Baylin, SB
通讯作者：
Baylin, SB
在结直肠癌患者上利用新开发的CpG岛甲基化微阵列的基因的甲基化谱。
影响因子：
14.9
作者：
Kimura, N;Nagasaka, T;Murakami, J;Sasamoto, H;Murakami, M;Tanaka, N;Matsubara, N
通讯作者：
Matsubara, N
影响因子：
--
作者：
Kerbel, R S
通讯作者：
Kerbel, R S
影响因子：
7.3
作者：
Kim, H;Kim, YH;Kim, H
通讯作者：
Kim, H
影响因子：
6
作者：
Lee, S;Lee, HJ;Kang, GH
通讯作者：
Kang, GH