Development of the diagnostic method to evaluate the risks for carcinogenesis, micro-metastasis, and malignant grade of oral cancer using in-house cDNA microarray

开发使用内部cDNA微阵列评估口腔癌的致癌、微转移和恶性程度风险的诊断方法

• 批准号: 13470427
• 负责人: TANZAWA Hideki
• 金额: $ 9.28万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470427/
• 关键词: DNA microarray; oral squamous cell carcinoma; diagnosis; risk for carcinogenesis; risk for micrometastasis; risk for malignant grade; 悪牲度評価; 口腔扁平上皮癌; microarray; 悪性度評価法

Our in-house cDNA microarray system, which carries cDNAs derived from oligo-capped cDNA library of human oral cavity cancer cell lines, identified several differentially expressed genes in tongue squamous cell carcinoma (SCC). Several genes were up-regulated 2-fold or higher in common among four tongue SCC specimens of independent cases, compared with normal tissues. Semiquantitative RT-PCR analysis confirmed these cDNA microarray findings. The up-regulated genes were C20orf21(AK000398), Interleukin 1 β (X56087), Centaurin gamma 2(AB029022), Adenylyl cyclase-associated protein (M98474), Rh type C glycoprotein (AF081497), Spermine syntase (AD001528), Copine 1 (U83246), KIAA0251 (AK025504), Clorf10, and Rab1a. The most differentially expressed gene, Rab1a, belongs to the member of the Ras oncogene family and was immunohistochemically studied for its protein expression in primary tongue SCC or leukoplakia, precancerous lesion, and corresponding normal tongue epithelium tissues. Immunohistochemical staining showed that Rab1a was differentially over-expressed in tongue SCC and leukoplakia tissues compared with normal oral epithelium ones. These results suggested that Rab1a is a candidate for an excellent tumor biomarker to evaluate the risks for carcinogenesis, micrometastasis, and malignant grade.

我们的内部基因芯片系统携带了来自口腔癌细胞系寡核苷酸文库的cDNAs，发现了几个舌鳞状细胞癌差异表达基因。与正常组织相比，4例独立病例的舌鳞状细胞癌组织中有几个基因的共同表达上调了2倍或更高。半定量RT-PCR分析证实了这些基因芯片的发现。上调的基因有C20orf21(AK000398)、IL-1β(X56087)、Centaurin Gamma 2(AB029022)、腺苷环化酶相关蛋白(M98474)、Rh C型糖蛋白(AF081497)、精胺合成酶(AD001528)、Copine 1(U83246)、KIAA0251(AK025504)、Clorf10和Rab1a。该基因属于RAS癌基因家族成员，免疫组织化学方法检测其在舌鳞癌或白斑、癌前病变及相应的正常舌上皮组织中的蛋白表达。免疫组织化学染色显示Rab1a在舌鳞状细胞癌和白斑组织中的表达明显高于正常口腔黏膜组织。这些结果表明，Rab1a是一个很好的肿瘤生物标志物，可以用来评估癌变、微转移和恶性程度的风险。