Alternative splicing of cancer-related genes in oral squamous cell carcinoma.

口腔鳞状细胞癌中癌症相关基因的选择性剪接。

• 批准号: 19390521
• 负责人: SUGIHARA Kazumasa
• 金额: $ 7.07万
• 依托单位: Kagoshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19390521/
• 关键词: 口腔癌; 予後因子; 分子標的治療; スプライシング; mRNA; 癌遺伝子; 癌抑制遺伝子; 口腔扁平上皮癌; 異常メチル化; p16; FHIT; E-cadherin; リンパ節転移; スプライシング異常; 口腔含嗽液; MUC1; MUC4; RT-PCR; 癌関連遺伝子

The purpose of the present study is to find markers, which might be molecules of targeted cancer therapy for the patients with oral squamous cell carcinoma(OSCC),by means of investigating the expression level of splicing isoforms of cancer-related genes in samples from patients with OSCC. The correlation between the expression level of several genes and clinicopathological factors was also evaluated. We harvested samples of the biopsy and operation in 107 patients with OSCC,and investigated the expression level of proteins of MUC1, MUC4, VEGF, and SULF2. Also mRNA expression of each cancer-related genes in the oral rinse obtained from 55 patients with OSCC was semi-quantitated by RT-PCR.The results obtained are as follows :I. The expression level of SULF2, MUC1 and MUC4 was significantly correlated with higher T classification, metastasis to regional lymph node, advanced tumor stage and poor prognosis. II. The expression levels of cancer-related genes were varied in each patient. III. The specific primer sets for MUC1, VEGF and VEGFR splicing variants were conducted, and those sensitivity and specificity were confirmed by using cultured cell. These results suggest that the expression level of SULF2, MUC1 and MUC4 gene might be the new useful prognostic factors of OSCC patients.

本研究的目的是通过研究口腔鳞状细胞癌(OSCC)标本中癌相关基因剪接异构体的表达水平，寻找有可能作为口腔鳞癌靶向治疗分子的标志物。并对几种基因的表达水平与临床病理因素的相关性进行了分析。我们收集了107例口腔鳞癌患者的活检和手术标本，检测了MUC1、MUC4、VEGF和SULF2蛋白的表达水平。用RT-PCR法半定量检测55例口腔鳞癌患者口腔含漱液中各癌相关基因的mRNA表达，结果如下：1.SULF2、MUC1和MUC4的表达水平与口腔鳞癌的T分期高、有无区域淋巴结转移、肿瘤分期高和预后不良有关。癌症相关基因的表达水平在每个患者中是不同的。III.针对MUC1、血管内皮生长因子和血管内皮生长因子受体的剪接变异体设计了特异的引物，并用培养细胞验证了其敏感性和特异性。提示SULF2、MUC1和MUC4基因的表达水平可能是口腔鳞癌患者新的有价值的预后指标。

项目成果

口腔含嗽液からの腫瘍抑制遺伝子プロモーター領域におけるDNA異常メチル化とヒストン修飾状態の検討

口腔含漱液抑癌基因启动子区DNA异常甲基化及组蛋白修饰状态检测

• 发表时间: 2008
• 作者: 楠元孝宣;浜田倫史;山田宗茂;後藤正道;米澤傑;向井洋;杉原一正
• 通讯作者: 杉原一正

MUC4ムチンの発現は口腔扁平上皮癌の予後予測因子となりうる

MUC4粘蛋白表达可能是口腔鳞状细胞癌的预后因素

• 发表时间: 2010
• 作者: 浜田倫史;若松常信;宮原麻由美;上村祐二;永田聡;野村昌弘;杉原一正
• 通讯作者: 杉原一正

口腔扁平上皮癌におけるムチン型糖タンパク質(MUC1、MUC4)発現の検討

口腔鳞状细胞癌中粘蛋白型糖蛋白（MUC1、MUC4）表达的检测

• 发表时间: 2008
• 作者: 浜田倫史;宮原麻由美;若松常信;楠元孝宣;上村祐二;永田聡;杉原一正
• 通讯作者: 杉原一正

口腔含嗽液からのDNAメチル化異常検出による口腔癌および発癌ハイリスク群スクリーニング法の確立

口腔含漱液DNA异常甲基化检测口腔癌及致癌高危人群筛查方法的建立

• 发表时间: 2008
• 作者: 浜田倫史;楠元孝宣;若松常信;向井洋;杉原一正
• 通讯作者: 杉原一正