使用组织微阵列对浸润性膀胱癌癌基因的研究

The Amplication and Overexpression of TRIO and its Correlation with Carcinogenesis and Bladder Cancer Growth

目的:比较基因杂交(CGH)研究发现染色体5p扩增与膀胱癌的发展有关;TRIO基因位于扩增区,其编码的蛋白在细胞周期调节中起主导作用。本研究在于了解TRIO的扩增和表达是否与膀胱癌的发展有关。方法:荧光原位杂交(FISH)、RNA原位杂交、NorthernBlot分析。结果:微小组织微阵列(TMA)FISH显示:12/14例膀胱癌组织显示TRIO扩增;含有1636例膀胱癌的组织微阵列FISH研究发现TRIO扩增与肿瘤浸润表现型、低分化密切相关。TRIO扩增仅见于1.5%早期膀胱肿瘤(pTaG1/G2)(7/456例),而在膀胱癌(pT1～4)高达12.8%(62/485例)。RNA原位杂交和NorthernBlot法证实TRIO在膀胱癌组织高表达。结论:TRIO扩增和高表达常发生在浸润性生长膀胱癌(pT1～4),可能在膀胱癌的发展过程中发挥重要作用。

Objective： To find out if amplification and overexpression of the TRIO gene, encoding a protein with a putative role in cell cycle regulation, is correlated to progression of bladder cancer because previous CGH analysis has shown that 5p amplification is linked to progression of bladder cancer and the TRIO gene maps to 5p15.1-p14. Methods： Fluorescence in situ hybridization （FISH）, RNA in situ hybridization and Northern blot analysis were used in this study. Results： FISH analysis of a small tissue microarray showed that the TRIO gene was included in the amplified area in 12 of 14 cases. Furthermore, the FISH study from a tissue microarray containing samples from 1636 bladder tumors suggested that TRIO amplification was closely associated with an invasive phenotype and poor differentiation of the tumor （P〈0.0001）. TRIO amplification can only be found in 1.5% （7 of 456） of cases with early stage pTaG1/G2 tumors, while it was found in 12.8% （62 of 485） of cases with pT1-4 bladder cancer. RNA in situ hybridization and Northern blot analysis confirmed that TRIO was overexpressed in tumors. Conclusion： TRIO is frequently anlplified and overexpressed in invasive bladder cancer （stage pT1-4）. The amplification and overexpression of TRIO may have a role in progression of bladder cancer.