Prediction of prognosis and clinical application of gene methylation score in urothelial cancers

尿路上皮癌基因甲基化评分的预后预测及临床应用

• 批准号: 18591761
• 负责人: NAKAGAWA Masayuki
• 金额: $ 2.51万
• 依托单位: Kagoshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 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-18591761/
• 关键词: gene methylation; urothelial cancer; bladder cancer; tumor suppressor gene; methylation score; prediction of prognosis; collagen type 1 A2; p16INK4a; p14ARF; DNA microarray法; 細胞周期関連遺伝子

Purpose : Many genes responsible for the bladder cancer progression have been isolated recently. We have reported thathypermethylation of 2 tumor suppressor genes, pl6INK4a and p14ARF is involved in poor prognosis and tumor invasiveness in patients with bladder cancer. In the present study, we examined methylation status of collagen 1A2 gene promoter region in terms of prediction of patient prognosis.Materials and Methods : We examined methylation status of collagen 1A2 gene in the presence and absence of demethylation agent, 5 aza-cytizine in human BOY cultured bladder cancer cells. We examined the frequency of methylation of collagen 1A2 gene in 97 clinical specimens from radical cystectomy and TURBT. Furthermore, we transfected collagen 1A2 gene into human bladder cancer cells and examined cell migration ability and growth rate in both transfectants and control cells.Results : Gene expression of collagen 1A2 gene was increased by 5 aza-cytizine treatment. Collagen 1A2 gene expression in bladder tumors was significantly lower than that in normal bladder tissues. Methylation scores in the bladder tumors are significantly higher that those in normal bladder tissues. Cell migration and growth rate in collagen 1A2 gene transfectants are significantly decreased compared to those in control cells.Conclusions : Collagen 1A2 gene expression is suppressed by the promoter methylation in human bladder cancers. These results suggest that collagen 1A2 gene plays a role in tumor suppressor in human bladder cancer.

目的：最近已经分离出许多负责膀胱癌进展的基因。我们已经报道说，在膀胱癌患者中，2种肿瘤抑制基因，PL6INK4A和P14ARF的非甲基化参与预后不良和肿瘤侵袭性。在本研究中，我们在预测患者预后的方面检查了胶原蛋白1a2基因启动子区域的甲基化状态。材料和方法：我们检查了在人类男孩培养的Bladder癌细胞中的5 AZA-胞嘧啶的存在和不存在脱甲基化剂的情况下胶原蛋白1a2基因的甲基化状态。我们检查了从自由基膀胱切除术和TURBT的97个临床标本中胶原蛋白1a2基因的甲基化频率。此外，我们将胶原蛋白1a2基因转染到人膀胱癌细胞中，并检查了转染剂和对照细胞中的细胞迁移能力和生长速率。分离：胶原蛋白1a2基因的基因表达增加了5 AZA-胞氨酸处理。膀胱肿瘤中胶原蛋白1a2基因表达明显低于正常膀胱组织中的胶原蛋白表达。膀胱肿瘤中的甲基化评分明显高于正常膀胱组织中的甲基化评分。与对照细胞中的细胞1a2基因转染剂中的细胞迁移和生长速率显着降低。结论：胶原蛋白1a2基因表达受到人膀胱癌中启动子甲基化的抑制。这些结果表明，胶原蛋白1a2基因在人膀胱癌中肿瘤抑制剂中起作用。

项目成果

Roles of collagen 1A2 gene methylation in bladder cancer

胶原1A2基因甲基化在膀胱癌中的作用

• 发表时间: 2007
• 作者: Mori;K;et. al.
• 通讯作者: et. al.

膀胱癌におけるCOL1A2遺伝子プロモーター領域のメチル化の検討

膀胱癌COL1A2基因启动子区甲基化检测

• 发表时间: 2007
• 作者: Kawakami;K;et. al.;吉田 正貴;森 勝久・他
• 通讯作者: 森 勝久・他

膀胱癌進展における遺伝子メチル化の役割

基因甲基化在膀胱癌进展中的作用

• 发表时间: 2007
• 作者: 榎田 英樹;ほか
• 通讯作者: ほか

Identification of differentially expressed genes in human bladder cancer through genome-wide gene expression profiling.

• DOI: 10.3892/or.16.3.521
• 发表时间: 2006-09
• 期刊: Oncology reports
• 影响因子: 4.2
• 作者: Kazumori Kawakami;H. Enokida;T. Tachiwada;T. Gotanda;Kengo Tsuneyoshi;H. Kubo;K. Nishiyama;M. Takiguchi-M.

膀胱癌におけるCOLIA2遺伝子プロモーター領域のメチル化の検討

膀胱癌COLIA2基因启动子区甲基化检测

• 发表时间: 2007
• 作者: 森 勝久;ほか
• 通讯作者: ほか