应用基因芯片技术筛查膀胱移行细胞癌差异表达基因的研究

Screening for differential-expressed genes in human transitional cell carcinoma of the bladder using gene chip

目的:研究膀胱移行细胞癌(BTCC)中差异表达基因,初步探讨这些基因与BTCC发生、发展的关系。方法:提取3例膀胱移行细胞癌(分别为G1Ta、G1T1和G2T2)组织块和1例正常膀胱黏膜组织块RNA,对样品RNA进行荧光标记,用包含21522条70mer长度的OligoDNA表达谱芯片3张进行检测。结果:21522条相关基因中,3例肿瘤标本共同出现的差异表达基因有307条,占总基因条数的1.42%,其中表达上调198条,表达下调109条。这些差异基因按其功能主要可以分为以下几类:原癌基因和抑癌基因、细胞周期调节蛋白、细胞信号和传递蛋白、细胞粘附分子、生长因子、免疫相关基因、细胞受体、离子通道和运输蛋白、细胞骨架和运动相关蛋白、细胞凋亡相关蛋白以及一些未知功能基因。结论:基因芯片技术为研究膀胱癌的分子生物学特性提供了一个比较理想的方法;膀胱癌的发生、发展与多个肿瘤相关基因的异常表达有关,是多基因、多途径作用的结果;BTCC明显表达异常的基因包括GJB2、DKFZP434K0410、NESCA、CKS2、ALB、MYOC、PCOLCE2、AREG、DPT等,其具体机制有待进一步研究。

Objective：To screen and identify the differential-expressed genes in bladder transitional cell carcinoma （BTCC） and investigate significance. Methods： Total RNA was isolated from 3 bladder tumor tissues（G1Ta, G1T1 and G2T2 ） and 1 normal bladder mucosal tissue respectively. RNA sample was labled with fluorescence dye. Four gene chips, every of which contains 21 522 70 mer Oligo DNA, were used to examine the differential-expressed genes. Result：Among 21 522 genes, 307（ 1.42 % ） differential-expressed genes were found in 3 tumor sample at the same time, including 198 up-regulated, and 109 down-regulated. Some main differential-expressed genes can be divided into categories with respect to founctions： proto-oncogene and anti-oncogene, cell cycle regulatory proteins, cellular signal and transferring proteins, cell adhesion molecules, growth factors （GF）, immune-associated genes, cell receptors, ion channels and transport proteins, cytoskeleton and motility-related proteins, apoptosis related proteins, and some unknown genes. Conclusion： The gene chip technique provides an ideal method for studying the biology characteristics of BTCC. The occurrence and progress of BTCC are related to aberrant expression of many tumor-related genes, and result from the interaction of many factors and pathways. The prominent abnormally expressed genes of BTCC are as follows： GJB2, DKFZP434K0410, NESCA, CKS2, ALB, MYOC, PCOLCE2,AREG,DPT and so on. Further research of mechanism are expected.