Rac1异常表达及变异与胃癌临床病理特征关系的研究

Abnormal expression and variation of Racl and their rela- tionship with clinicopathology of gastric carcinoma

目的研究Ras相关的C3肉毒素底物1（Rac1）表达及变异，探讨其与胃癌生物学行为的关系。方法以Rac1 mRNA为标志基因，用RT-PCR方法检测66例患者胃癌组织、癌旁组织、11例胃良性病变中Rac1 mRNA的表达情况。应用PCR-SSCP方法显示Rac1基因存在的变异。结果66例胃癌患者的癌和癌旁组织中Rac1 mRNA表达阳性率分别为81．82％、27．27％，两组差异显著（X^2=39．6，P=0．001）。11例胃良性病变中无Rac1mRNA的表达。胃癌组织中Rac1 mRNA平均表达水平（Md=1．641，Q75=1．967）明显高于癌旁组织（Md=0，Q75=0．024），两者差异有显著性（P〈0．01）。无转移组、微转移组和转移组中Rac1 mRNA表达阳性率分别为22．22％、88．67％和92．86％，三组差异显著（X^2=25．165，P=0．000）。微转移和转移组中Rac1 mRNA平均表达水平明显高于无转移组，三组差异有显著性（X^2=14．577，P=0．0007）。Rac1在不同临床分期、分化程度和胃癌淋巴结转移及微转移的标本中的阳性表达率比较，差异有显著性意义（P〈0．05）。3份超水平表达Rac1的PCR产物在非变性胶中出现了明显不同的染色区带，表明它们的Rac1表达产物存在基因变异。结论Rac1 mRNA的高表达以及变异与胃癌临床病理表现密切相关，为胃癌基因治疗提供了新的靶点。

Objective To investigate the relationship between expression and variation of rasrelated C3 botulinum toxin substrate, Racl, and biological behaviours of gastric cancer. Methods 66 cases of gastric cancer were divided into 3 groups, of metastasis, of micrometastasis, and no metastasis, in terms of pathological examination and CK18 expression; with 11 benign gastric diseases as the control in the study. Racl expression in mucosal samples were detected by reverse transcription-polymerase chain reaction （RT-PCR）. PCR-SSCP was performed to find the variation in Racl transcripts. Results Positive rate of Racl expression in gastric cancer tissues was 81.82%, compared to 7.27% only in para-cancer tissues with significant difference （X^2=39.6, P =0. 001）. There was no Racl mRNA expression in iI cases of benign gastric lesion. Expressing level of Racl mRNA in cancer tissues was much higher than in para-cancer tissues,（l.641 vs 0 of Md, P〈0.01）. Positive rate of Racl expression in nonmetastasis, micrometastasis and metastasis were 22.22%, 88.67% and 92.86% with significant difference. （X^2=25. 165, P=0. 000）. Expressing level of Racl mRNA in in micrometastasis and metastasis were much higher than in nonmetastasis, with significant difference （X^2=14.577, P=0. O007） . There were significant differences found in expression of Racl among the different clinical stages and of tumor with metastases compared those without metastases （P〈O. 05）. 3 RT-PCR products with the highest- Racl expressing were shown to exhibit unique SSCP profile. Conclusion Super expression, and variation of Racl may be concerned in development and metachoresis of gastric carcinoma and provide with a novel target for gene therapy.