The study of roles of Rho family GTPase in progression and metastasis of renal cell cancer

采用逆转录后聚合酶链式反应(RT-PCR)技术检测78例日本肾癌手术标本和相应的非肿瘤组织中RhoA、RhoB、RhoC和ROCK基因的表达水平。我们比较了它们在肿瘤组织和非肿瘤组织中的表达水平，并探讨了它们在肿瘤组织中的表达水平与临床病理特征的关系。与切除的非肿瘤组织相比，肿瘤组织中RhoC和ROCK的基因表达水平升高(分别为P&lt；0.0001，P&lt；0.0001)。RhoA的mRNAs表达水平无明显差异。虽然RhoB在肿瘤组织中的表达水平高于非肿瘤组织(P&lt；0.05)，但其表达与肿瘤的分级、分期及预后无关。RhoC和ROCK基因表达水平的升高与肿瘤分级(P<0.05)和S…有关更多的Tage(分别为P&lt；0.0001和P&lt；0.0001)。肿瘤组织中RhoC和ROCK的mRNAs表达水平呈正相关(P&lt；0.0001)。在Rhoc和ROCK基因表达水平低和高表达的患者中，生存率的Kaplan-Meier曲线图显示，RhoC和ROCK基因表达水平高与总生存期相关(P&lt；0.0001，P&lt；0.0001)。多因素分析显示，RhoA、RhoC和ROCK的表达水平是影响患者总体生存的独立预后因素，RhoA和ROCK蛋白的高表达与肾癌的低分化程度、高分期和不良预后相关1)。在膀胱癌中，虽然RhoA、RhoC和ROCK的高蛋白表达与低分化程度、高分期和不良预后有关，但在晚期肿瘤中RhoB的表达水平较低。较少

We analyzed the mRNA levels of RhoA, RhoB, RhoC and ROCK gene in the surgical specimens of RCC tissues from 78 consecutive Japanese patients and in the corresponding non-tumor tissue originating from the same patient using polymerase chain reaction after reverse transcription (RT-PCR). We compared their expression levels in tumor tissues with those in non-tumor tissues and evaluated the relationship between their expression levels in tumors and clinicopathological features.The mRNA levels of RhoC and ROCK were increased in tumor tissues, compared with those in non-tumor tissues of the resected testis (P<0.0001, P<0.0001, respectively). There was no difference between the expression levels of mRNAs for RhoA. Although RhoB mRNA levels were higher in tumor tissues than those in non-tumor tissues (P<0.05), its expression was not associated with tumor grade, stage and prognosis. The increase of the RhoC and ROCK mRNA levels was related to the tumor grade (P<0.05, P<0.05, respectively) and s … More tage (P<0.0001, P<0.0001, respectively). There was a positive relationship between expression levels of mRNAs of RhoC and ROCK in tumor tissues (P<0.0001). Kaplan-Meier plots of survival rate in patients with low versus high mRNA levels of RhoC and ROCK showed that high mRNA levels of RhoC and ROCK were associated with overall survival (P<0.0001, P<0.0001, respectively). Multivariate analysis showed that mRNA levels of RhoC and ROCK were independent prognostic factors in overall survival.In renal pelvis and ureter cancer, the higher expression of RhoA and ROCK proteins were associated poorly differentiated grade, higher stage, and unfavorable prognosis 1).In bladder cancer, although the higher protein levels of RhoA, RhoC, and ROCK were related to poorly differentiated grade, higher stage, and unfavorable prognosis, the lower RhoB levels were shown in advanced tumors 2).In testicular germ cell tumor, the higher expressions of RhoA, ROCK, Rac1 and Cdc42 were associated with advanced stage of the disease 3). Less