Development of diagnostic methods of gastrointestinal cancer using integrated analysis of nuclear molecules

利用核分子整合分析开发胃肠癌诊断方法

• 批准号: 18390221
• 负责人: SHINOMURA Yasuhisa
• 金额: $ 11.03万
• 依托单位: Sapporo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18390221/
• 关键词: gastrointestinal cancer; methylation; epigenetics; genetic diagnosis; prediction of cancer risk; 遺伝子不安定性; 遺伝子変異; 前癌病変

The molecular mechanism by which H. pylori infection leads to gastric cancer is not fully understood. Similarly, patients with enlarged fold gastritis, one cause of which is H. pylori infection, have an increased risk of gastric cancer, though again molecular mechanism is unclear. In the present study, we analyzed the methylation status of LINE-1 and three cancer-related genes in a panel of gastric mucosae, with or without enlarged fold gastritis. We used bisulfite-pyrosequencing to assess the levels of LINE-1, CDH1, CDH13 and PGP9.5 methylation in 78 gastric mucosa specimens from 48 patients. Levels of LINE-1 methylation were significantly reduced in mucosae from patients with enlarged fold gastritis. This hypomethylation of LINE-1 was associated with increased methylation of the 5' CpG islands of the genes, which suggests that, in enlarged fold gastritis, methylation of the promoter regions of certain genes is accompanied by global demethylation of repetitive sequences. Our results indicate that genome-wide hypomethylation and regional hypermethylation occur in enlarged fold gastritis and may contribute to the tumorigenesis of diffuse type gastric cancers.

幽门螺杆菌感染导致胃癌的分子机制尚不完全清楚。同样，患有肥厚性胃炎（其原因之一是幽门螺杆菌感染）的患者患胃癌的风险增加，尽管分子机制尚不清楚。在本研究中，我们分析了一组胃粘膜中 LINE-1 和三个癌症相关基因的甲基化状态，无论是否患有扩大性胃炎。我们使用亚硫酸氢盐-焦磷酸测序来评估 48 名患者的 78 份胃粘膜标本中的 LINE-1、CDH1、CDH13 和 PGP9.5 甲基化水平。肥厚性胃炎患者粘膜中的 LINE-1 甲基化水平显着降低。 LINE-1 的低甲基化与基因 5' CpG 岛甲基化的增加有关，这表明，在扩大的皱襞胃炎中，某些基因的启动子区域的甲基化伴随着重复序列的整体去甲基化。我们的结果表明，肥大性胃炎中发生全基因组低甲基化和区域高甲基化，并可能导致弥漫型胃癌的肿瘤发生。

项目成果

Treatment with IGF-I receptor tyrosine kinase inhibitor, NVP-AEW541, for gastrointestinal carcinomas.

使用 IGF-I 受体酪氨酸激酶抑制剂 NVP-AEW541 治疗胃肠道癌。

• 发表时间: 2007
• 作者: Adachi Y;et. al.
• 通讯作者: et. al.

Ku70 and poly(ADP-ribose)polymerase-1 competitively regulate beta-catenin and T-cell factor-4-mediafed gene transactivation:possible linkage of DNA damage

Ku70和聚（ADP-核糖）聚合酶-1竞争性调节β-连环蛋白和T细胞因子4介导的基因反式激活：DNA损伤的可能联系

• 发表时间: 2007
• 期刊: Cancer Res. 67
• 作者: Idogawa M K;et. al.
• 通讯作者: et. al.

Recent Advances in Gastrointestinal Carcinogenesis

胃肠癌发生的最新进展

• 发表时间: 2006
• 作者: Higashi;H.
• 通讯作者: H.

Differential expression of angiogenesis-related genes in human gastric cancers with and those without high-frequency microsatellite instability

• DOI: 10.1016/j.canlet.2007.02.004
• 发表时间: 2007-08-28
• 期刊: CANCER LETTERS
• 影响因子: 9.7
• 作者: Miyamoto, Nobuki;Yamamoto, Hiroyuki;Shinomura, Yasuhisa
• 通讯作者: Shinomura, Yasuhisa

IGF-I receptor is a candidate molecurar target for both human esophageal squamous cell carcinoma and adenocarcinoma.

IGF-I 受体是人食管鳞状细胞癌和腺癌的候选分子靶点。

• 发表时间: 2007
• 作者: Adachi Y;et. al.
• 通讯作者: et. al.