Molecular analysis of gastric differentiated-type intramucosal and submucosal cancers
Molecular analysis of gastric differentiated-type intramucosal and submucosal cancers
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DOI：
10.1002/ijc.25271
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发表时间：
2010-12-01
影响因子：
6.4
通讯作者：
Suzuki, Kazuyuki
中科院分区：
文献类型：
--
作者：
Sugai, Tamotsu;Habano, Wataru;Suzuki, Kazuyuki
粘膜内癌（IMC）和粘膜下癌（SMCs）的分子特征的鉴定对于我们理解早期胃癌的发生至关重要。然而，关于这两种病变之间的差异知之甚少。对148例早期胃癌患者进行了细胞周期相关蛋白表达和杂合性缺失（洛）的检测，其中IMC 106例，SMC 421例。我们还检查了微卫星不稳定性（MSI）和甲基化状态。对于洛缺失和甲基化研究，我们使用了一组17个微卫星标记（3 p，4p，5 q，9 p。13 q、17 p、18 q和22 q）和9个基因（MLH-1、RUNX 3、p16、HPP 1、RASSF 2A、SFRP 1、DKK-1、ZFP 64和SALL 4）的启动子区，这些基因在胃癌中经常发生改变或甲基化。SMC中p53和cyclin D1蛋白表达增强。此外，p27低表达在SMC中比在IMC中更常见。SMC中4p、9 p、13 q和22 q的频率显著高于IMC。SALL 4基因在SMC中甲基化频率高于IMC。然而，其他基因甲基化是常见的IMC和SMC。SMC中LOH高/甲基化低的频率显著高于IMC。SMC LOH-低/甲基化-高状态在IMC中更常见。我们的数据证实了癌症相关基因的甲基化在IMC的发展中起着重要作用。重要的是，这些结果还表明，胃粘膜下进展的特征是特定遗传改变的积累。此外，细胞周期相关蛋白的变化与癌症进展相关。
Identification of the molecular characteristics of intramucosal (IMCs) and submucosal cancers (SMCs) is essential to our understanding of early gastric carcinogenesis. However, little is known regarding the differences between the 2 lesions. One hundred and forty-eight patients with primary early gastric cancer [IMC, 106; SMC, 421 were characterized for expression of cell cycle-related proteins and loss of heterozygosity (LOH). We also examined microsatellite instability (MSI) and methylation status. For LOH and methylation studies, we used a panel of 17 microsatellite markers (3p, 4p, 5q, 9p. 13q, 17p, 18q and 22q) and promoter regions of 9 genes (MLH-1, RUNX3, p16, HPP1, RASSF2A, SFRP1, DKK-1, ZFP64 and SALL4) that are frequently altered or methylated in gastric cancers. Overexpression of p53 and cyclin D1 was observed in SMC. In addition, low expression of p27 was more frequent in SMC than in IMC. Frequencies of 4p, 9p, 13q and 22q were significantly higher in SMC than in IMC. The SALL4 gene was frequently methylated in SMC compared with IMC. However, other gene methylations were common in both IMC and SMC. The frequency of LOH-high status/methylation-low status was significantly higher in SMC than in IMC. However, LOH-low status/methylation-high status in SMC was more frequently found in IMC. Our data confirm that nnethylation of cancer-related genes plays a major rote in the development of IMCs. Importantly, the results also show that gastric submucosal progression is characterized by the accumulation of specific genetic alterations. In addition, changes of cell cycle-related proteins are associated with cancer progression.